Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics.

PubMed

Shin, Gunchul; Gomez, Adrian M; Al-Hasani, Ream; Jeong, Yu Ra; Kim, Jeonghyun; Xie, Zhaoqian; Banks, Anthony; Lee, Seung Min; Han, Sang Youn; Yoo, Chul Jong; Lee, Jong-Lam; Lee, Seung Hee; Kurniawan, Jonas; Tureb, Jacob; Guo, Zhongzhu; Yoon, Jangyeol; Park, Sung-Il; Bang, Sang Yun; Nam, Yoonho; Walicki, Marie C; Samineni, Vijay K; Mickle, Aaron D; Lee, Kunhyuk; Heo, Seung Yun; McCall, Jordan G; Pan, Taisong; Wang, Liang; Feng, Xue; Kim, Tae-Il; Kim, Jong Kyu; Li, Yuhang; Huang, Yonggang; Gereau, Robert W; Ha, Jeong Sook; Bruchas, Michael R; Rogers, John A

2017-02-08

In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source, limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin, flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable light-emitting diodes (LEDs), with the ability to operate at wavelengths ranging from UV to blue, green-yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Flexible near field wireless optoelectronics as subdermal implants for broad applications in optogenetics

PubMed Central

Shin, Gunchul; Gomez, Adrian M.; Al-Hasani, Ream; Jeong, Yu Ra; Kim, Jeonghyun; Xie, Zhaoqian; Banks, Anthony; Lee, Seung Min; Han, Sang Youn; Yoo, Chul Jong; Lee, Jong-Lam; Lee, Seung Hee; Kurniawan, Jonas; Tureb, Jacob; Guo, Zhongzhu; Yoon, Jangyeol; Park, Sung-Il; Bang, Sang Yun; Nam, Yoonho; Walicki, Marie C.; Samineni, Vijay K.; Mickle, Aaron D.; Lee, Kunhyuk; Heo, Seung Yun; McCall, Jordan G.; Pan, Taisong; Wang, Liang; Feng, Xue; Kim, Taeil; Kim, Jong Kyu; Li, Yuhang; Huang, Yonggang; Gereau, Robert W.; Ha, Jeong Sook; Bruchas, Michael R.; Rogers, John A.

2017-01-01

Summary In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable LEDs, with the ability to operate at wavelengths ranging from ultraviolet to blue, green/yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications. PMID:28132830

Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.

PubMed

Hognert, Helena; Kopp Kallner, Helena; Cameron, Sharon; Nyrelli, Christina; Jawad, Izabella; Heller, Rebecca; Aronsson, Annette; Lindh, Ingela; Benson, Lina; Gemzell-Danielsson, Kristina

2016-11-01

Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion? A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion. The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known. This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat. Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland. Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018. For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis. Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days. This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare. ClinicalTrials number NCT01920022. 06 August 2013. 13 October 2013. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A 12-month multicenter, randomized study comparing the levonorgestrel intrauterine system with the etonogestrel subdermal implant.

PubMed

Apter, Dan; Briggs, Paula; Tuppurainen, Marjo; Grunert, Julia; Lukkari-Lax, Eeva; Rybowski, Sarah; Gemzell-Danielsson, Kristina

2016-07-01

To compare the levonorgestrel intrauterine system (LNG-IUS 8), which has an average levonorgestrel release rate of ∼8 μg/24 hours during the first year (total levonorgestrel content 13.5 mg; Jaydess/Skyla), with the etonogestrel (ENG) subdermal implant (total content, 68 mg) with regard to the 12-month discontinuation rate (primary outcome). Randomized, open-label, phase III study. Thirty-eight centers in six European countries. Study population of 766 healthy nulliparous and parous women aged 18-35 years. The LNG-IUS 8 or the ENG implant. Discontinuation rate, by treatment group, at Month 12. The 12-month discontinuation rates were 19.6% and 26.8% in the LNG-IUS 8 and ENG implant groups, respectively. The -7.2% difference was statistically significant (95% confidence interval -13.2%, -1.2%). Fewer women in the LNG-IUS 8 group than in the ENG implant group discontinued because of increased bleeding (3.2% vs. 11.3%) or adverse events (14.3% vs. 21.8%). At 12 months, more women in the LNG-IUS 8 group than in the ENG implant group were "very/somewhat satisfied" with their bleeding pattern (60.9% vs. 33.6%) and reported a preference to use their study treatment after study completion (70.1% vs. 58.5%). The LNG-IUS 8 was associated with a significantly lower 12-month discontinuation rate compared with the ENG implant; mainly because ENG implant users frequently discontinued due to increased bleeding. More LNG-IUS 8 users than ENG implant users reported being "very/somewhat satisfied" with their bleeding pattern, and reported a preference to continue using their study treatment after the study. NCT01397097. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Introduction of the levonorgestrel intrauterine system in Kenya through mobile outreach: review of service statistics and provider perspectives.

PubMed

Hubacher, David; Akora, Vitalis; Masaba, Rose; Chen, Mario; Veena, Valentine

2014-02-01

The levonorgestrel intrauterine system (LNG IUS) was developed over 30 years ago, but the product is currently too expensive for widespread use in many developing countries. In Kenya, one organization has received donated commodities for 5 years, providing an opportunity to assess impact and potential future role of the product. We reviewed service statistics on insertions of the LNG IUS, copper intrauterine device (IUD), and subdermal implant from 15 mobile outreach teams during the 2011 calendar year. To determine the impact of the LNG IUS introduction, we analyzed changes in uptake and distribution of the copper IUD and subdermal implant by comparing periods of time when the LNG IUS was available with periods when it was not available. In addition, we interviewed 27 clinicians to assess their views of the product and of its future role. When the LNG IUS was not available, intrauterine contraception accounted for 39% of long-acting method provision. The addition of the LNG IUS created a slight rise in intrauterine contraception uptake (to 44%) at the expense of the subdermal implant, but the change was only marginally significant (P = .08) and was largely attributable to the copper IUD. All interviewed providers felt that the LNG IUS would increase uptake of long-acting methods, and 70% felt that the noncontraceptive benefits of the product are important to clients. The LNG IUS was well-received among providers and family planning clients in this population in Kenya. Although important changes in service statistics were not apparent from this analysis (perhaps due to the small quantity of LNG IUS that was available), provider enthusiasm for the product was high. This finding, above all, suggests that a larger-scale introduction effort would have strong support from providers and thus increase the chances of success. Adding another proven and highly acceptable long-acting contraceptive technology to the method mix could have important reproductive health impact.

Axillary migration of Nexplanon®: Case report.

PubMed

Diego, Daniela; Tappy, Erryn; Carugno, Jose

2017-02-01

A 19-year-old patient presented to the clinic, and we inserted a single rod subdermal etonogestrel implant (Nexplanon ®), which subsequently migrated to the ipsilateral axilla. Distant Nexplanon® migration is a rare serious complication that should be considered when a device is nonpalpable. Management options are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

76 FR 62419 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... Agency's Web site and call the appropriate advisory committee hot line/phone line to learn about possible... wrinkles in the face. The AQUAMID dermal filler is intended for use in mid-to-deep sub-dermal implantation... before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting...

Triglycidylamine Crosslinking of Porcine Aortic Valve Cusps or Bovine Pericardium Results in Improved Biocompatibility, Biomechanics, and Calcification Resistance

PubMed Central

Connolly, Jeanne M.; Alferiev, Ivan; Clark-Gruel, Jocelyn N.; Eidelman, Naomi; Sacks, Michael; Palmatory, Elizabeth; Kronsteiner, Allyson; DeFelice, Suzanne; Xu, Jie; Ohri, Rachit; Narula, Navneet; Vyavahare, Narendra; Levy, Robert J.

2005-01-01

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH3. TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance. PMID:15631995

Embolization of a contraceptive implant into the pulmonary vasculature in an adolescent female.

PubMed

Gao, Gabriel T; Binder, William

2018-06-01

Nexplanon is a long-acting 4cm radio-opaque rod shaped contraceptive device implanted in the subdermal layer of the inner, upper arm. Complications from implantation are uncommon and mostly local and minor, including infection at the implantation site with resulting cellulitis or abscess, hematoma, abnormal scar formation, or local damage to nerves and blood vessels. Intravascular insertion is estimated to be at 1.3 per million Nexplanon implants, and migration and embolization is a rare complication of this device. We present a case report of a 16year old female who presented to the pediatric emergency department with subjective dyspnea and an embolized contraceptive device within a subsegmental branch of the left lower lobe pulmonary artery. After discussion with consultants, interventional radiology was able to successful retrieve the device without complication. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased negatively of interstitial fluid pressure in rat skin contributes to the edema formation induced by Zymosan.

PubMed

Ostgaard, G; Reed, R K

1993-11-01

Increased negatively of interstitial fluid pressure (Pif) contributes to rapid edema formation in several acute inflammatory reactions attesting to an "active" role for the loose connective tissues in the transcapillary fluid exchange and edema formation under these circumstances. The present study reports the effect of the complement activator Zymosan on Pif, transcapillary fluid, and albumin flux. Micropipettes (tip diameter 5 to 7 microns) connected to a servo-controlled counterpressure system were used to measure Pif in rat dermis. When compared to saline injection, subdermal injection of 1 mg Zymosan in 10 microliters 0.15 M NaCl increased total tissue water by 1.6 ml/g dry weight in 5 min, corresponding to about 150% increase in interstitial fluid volume. Pif increased from +0.4 to +3.7 mm Hg. Increased negativity of Pif can be masked by the edema formation which will increase Pif. Measurements were therefore also performed after circulatory arrest, when transcapillary fluid flux and edema formation are abolished. Using this experimental protocol Pif fell from +0.3 mm Hg to -2.5 mm Hg 5 min after subdermal injection of Zymosan and remained at this level throughout the observation period of 90 min. Injection of saline alone after circulatory arrest increased Pif transiently by about 1 mm Hg. Thus, subdermal injection of Zymosan causes increased negativity of Pif by about 4 mm Hg. Although the lowering of Pif itself will explain a minor part of the increased fluid filtration, the results attest to the role of loose connective tissues being active in the edema-generating process also in the inflammatory reaction induced by Zymosan.

Sequential hydrophile and lipophile solubilization as an efficient method for decellularization of porcine aortic valve leaflets: Structure, mechanical property and biocompatibility study.

PubMed

Qiao, Wei-Hua; Liu, Peng; Hu, Dan; Al Shirbini, Mahmoud; Zhou, Xian-Ming; Dong, Nian-Guo

2018-02-01

Antigenicity of xenogeneic tissues is the major obstacle to increased use of these materials in clinical medicine. Residual xenoantigens in decellularized tissue elicit the immune response after implantation, causing graft failure. With this in mind, the potential use is proposed of three protein solubilization-based protocols for porcine aortic valve leaflets decellularization. It was demonstrated that hydrophile solubilization alone achieved incomplete decellularization; lipophile solubilization alone (LSA) completely removed all cells and two most critical xenoantigens - galactose-α(1,3)-galactose (α-Gal) and major histocompatibility complex I (MHC I) - but caused severe alterations of the structure and mechanical properties; sequential hydrophile and lipophile solubilization (SHLS) resulted in a complete removal of cells, α-Gal and MHC I, and good preservation of the structure and mechanical properties. In contrast, a previously reported method using Triton X-100, sodium deoxycholate and IGEPAL CA-630 resulted in a complete removal of all cells and MHC I, but with remaining α-Gal epitope. LSA- and SHLS-treated leaflets showed significantly reduced leucocyte activation (polymorphonuclear elastase) upon interaction with human blood in vitro. When implanted subdermally in rats for 6 weeks, LSA- or SHLS-treated leaflets were presented with more biocompatible implants and all four decellularized leaflets were highly resistant to calcification. These findings illustrate that the SHLS protocol could be considered as a promising decellularization method for the decellularization of xenogeneic tissues in tissue engineering and regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Low-Power, 8-Channel EEG Recorder and Seizure Detector ASIC for a Subdermal Implantable System.

PubMed

Do Valle, Bruno G; Cash, Sydney S; Sodini, Charles G

2016-12-01

EEG remains the mainstay test for the diagnosis and treatment of patients with epilepsy. Unfortunately, ambulatory EEG systems are far from ideal for patients who have infrequent seizures. These systems only last up to 3 days and if a seizure is not captured during the recordings, a definite diagnosis of the patient's condition cannot be given. This work aims to address this need by proposing a subdermal implantable, eight-channel EEG recorder and seizure detector that has two modes of operation: diagnosis and seizure counting. In the diagnosis mode, EEG is continuously recorded until a number of seizures are recorded. In the seizure counting mode, the system uses a low-power algorithm to track the number of seizures a patient has, providing doctors with a reliable count to help determine medication efficacy or other clinical endpoint. An ASIC that implements the EEG recording and seizure detection algorithm was designed and fabricated in a 0.18 μm CMOS process. The ASIC includes eight EEG channels and is designed to minimize the system's power and size. The result is a power-efficient analog front end that requires 2.75 μW per channel in diagnosis mode and 0.84 μW per channel in seizure counting mode. Both modes have an input referred noise of approximately 1.1 μVrms.

Lessons learnt from the introduction of the contraceptive implant in South Africa

PubMed

Pleaner, M; Morroni, C; Smit, J; Lince-Deroche, N; Chersich, M; Mullick, S; Pillay, D; Makua, M; Rees, H

2017-10-01

In 2014, South Africa (SA) introduced the subdermal contraceptive implant with the aim of expanding the contraceptive method mix and availability of long-acting reversible methods in the public sector. Three years on, concerns have been raised about the decline in uptake, early implant removals and challenges in service delivery. This article explores the lessons learnt from the introduction of contraceptive technologies elsewhere and applies these to the SA context. Drawing on the World Health Organization’s conceptual framework for the introduction of new contraceptive methods, and subsequent literature on the topic, lessons are classified into six cross-cutting themes. Recommendations highlight the need for SA to review and explore strategies to strengthen current implant services, including the provision of improved provider training aimed at sensitive, client-centred approaches; increased community engagement; and improved systems for programmatic monitoring and evaluation. With implementation of these recommendations, worrying trends in the provision of implants could be reversed. Creative Commons Attribution - NonCommercial Works License (CC BY-NC 4.0)

Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

PubMed Central

Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

2015-01-01

Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

Vascularization and tissue infiltration of a biodegradable polyurethane matrix

PubMed Central

Ganta, Sudhakar R.; Piesco, Nicholas P.; Long, Ping; Gassner, Robert; Motta, Luis F.; Papworth, Glenn D.; Stolz, Donna B.; Watkins, Simon C.; Agarwal, Sudha

2016-01-01

Urethanes are frequently used in biomedical applications because of their excellent biocompatibility. However, their use has been limited to bioresistant polyurethanes. The aim of this study was to develop a nontoxic biodegradable polyurethane and to test its potential for tissue compatibility. A matrix was synthesized with pentane diisocyanate (PDI) as a hard segment and sucrose as a hydroxyl group donor to obtain a microtextured spongy urethane matrix. The matrix was biodegradable in an aqueous solution at 37°C in vitro as well as in vivo. The polymer was mechanically stable at body temperatures and exhibited a glass transition temperature (Tg) of 67°C. The porosity of the polymer network was between 10 and 2000 µm, with the majority of pores between 100 and 300 µm in diameter. This porosity was found to be adequate to support the adherence and proliferation of bone-marrow stromal cells (BMSC) and chondrocytes in vitro. The degradation products of the polymer were nontoxic to cells in vitro. Subdermal implants of the PDI–sucrose matrix did not exhibit toxicity in vivo and did not induce an acute inflammatory response in the host. However, some foreign-body giant cells did accumulate around the polymer and in its pores, suggesting its degradation is facilitated by hydrolysis as well as by giant cells. More important, subdermal implants of the polymer allowed marked infiltration of vascular and connective tissue, suggesting the free flow of fluids and nutrients in the implants. Because of the flexibility of the mechanical strength that can be obtained in urethanes and because of the ease with which a porous microtexture can be achieved, this matrix may be useful in many tissue-engineering applications. PMID:12522810

Female adolescents' compliance with contraceptive regimens.

PubMed

Jay, M S; DuRant, R H; Litt, I F

1989-06-01

Although today's adolescents have access to a variety of contraceptive options, they remain inconsistent and suboptimal users of these methods. A particularly frustrating problem for those caring for adolescents is the issue of noncompliance with contraceptives, which is an important antecedent of adolescent pregnancy. In the future, new fertility-related developments such as subdermal hormonal implants may reduce the likelihood of noncompliance. For the present, however, systematic monitoring rather than only when noncompliance is suspected is essential in enhancing adolescents' contraceptive compliance.

Testicular heat exposure enhances the suppression of spermatogenesis by testosterone in rats: the "two-hit" approach to male contraceptive development.

PubMed

Lue, Y; Hikim, A P; Wang, C; Im, M; Leung, A; Swerdloff, R S

2000-04-01

The objectives of the study were to determine stage-specific changes in the kinetics of germ cell apoptosis induced by administration of exogenous testosterone (T) alone and to examine whether addition of a single testicular heat exposure would enhance the induction of germ cell apoptosis and the suppression of spermatogenesis by T. Adult male rats were implanted with 3-cm SILASTIC brand capsules (Dow Corning Corp.) containing T for up to 6 weeks. Intratesticular T levels declined to 2.9% of control values by 1 week and remained suppressed at 2, 3, and 6 weeks after T administration. The incidence of germ cell apoptosis (expressed as numbers per 100 Sertoli cells) was low in control rats (0-9.52). After T treatment, the mean incidence of apoptosis at stages VII-VIII increased significantly by 1 week (21.43 +/-3.33) and showed further increases by 6 weeks (56.30 +/- 7.47); apoptotic rates remained low at early (I-VI) and later (XII-XIV) stages. To test whether the combination of T with a single testicular heat exposure resulted in more complete suppression of spermatogenesis than either treatment alone, four groups of adult rats received one of the following treatments: 1) a subdermal empty polydimethylsilozane implant, 2) exposure to a single testicular heating (43 C for 15 min) applied on day 14, 3) 3-cm T implant, or 4) 3-cm T implant and a single testicular heat exposure (applied on day 14). All animals were killed at the end of 6 weeks. In the heat-treated group, testis weight and testicular sperm counts were decreased to 65.4% and 28.9% of control levels, respectively. The corresponding values in the T-treated group were 49.7% and 24.9% of control levels, respectively. Notably, addition of heat to T further reduced testis weight to 31.1% of control levels and testicular sperm counts to near zero. Histomorphometric analysis showed that all treatments reduced seminiferous tubular diameter and epithelial and luminal volume, with the greatest decrease after combined T and heat treatment. Heat exposure in animals bearing T implants markedly reduced the number of pachytene spermatocytes and round spermatids through apoptosis, resulting in tubules devoid of mature spermatids. Spermatogonia and preleptotene spermatocytes remained unaffected. These results clearly demonstrate that 1) exogenous T reduces intratesticular T and induces apoptosis mainly at stages VII-VIII within 1-6 weeks; 2) the combined treatment of T and heat markedly inhibits spermatogenesis, resulting in near azoospermia within 6 weeks; and 3) meiosis and spermiogenesis are the most vulnerable phases of spermatogenesis in response to T plus heat treatment. These findings suggest that a combination of hormonal treatment such as T and a physical agent (heat exposure) is more effective in suppressing spermatogenesis than either treatment alone. We hypothesize that combination of two antispermatogenic agents ("two hit") working at separate stages of the spermatogenic cycle will lead to greater male contraceptive efficacy.

Safety, Quality, and Acceptability of Contraceptive Subdermal Implant Provision by Community Health Extension Workers Versus Nurses and Midwives in Nigeria: Protocol for a Quasi-Experimental, Noninferiority Study

PubMed Central

Penfold, Suzanne; Alabi, Olalere; Ali, Moazzam; Hopkins, Kristen; Ngo, Thoai Dinh; Odogwu, Kingsley; Douthwaite, Megan; Ezire, Onoriode; Udoh, Uko; Effiom, Effiom; Munroe, Erik S

2018-01-01

Background As part of its Family Planning 2020 commitment, the Nigerian government is aiming for a contraceptive prevalence rate of 36% by 2018, and in 2014, approved a policy to allow community health extension workers (CHEWs), in addition to doctors, nurses, and midwives, to provide contraceptive subdermal implants. There is a lack of rigorous evidence on the safety of long-acting reversible contraceptive provision, such as implants, among lower cadres of health providers. Objective This study aimed to compare implant provision by CHEWs versus nurses and midwives up to 14 days post insertion. Methods The quasi-experimental, noninferiority study will take place in public sector facilities in Kaduna and Ondo States. In each state, we will select 60 facilities, and from these, we will select a total of 30 nurses and midwives and 30 CHEWs to participate. Selected providers will be trained to provide implant services. Once trained, providers will recruit a minimum of 8125 women aged between 18 and 49 years who request and are eligible for an implant, following comprehensive family planning counseling. During implant insertion, providers will record data about the process and any adverse events, and 14 days post insertion, providers will ask 4410 clients about adverse events arising from the implant. Supervisors will observe 792 implant insertions to assess service provision quality and ask clients about their satisfaction with the procedure. We will conclude noninferiority if the CI for the difference in the proportion of adverse events between CHEWs and nurses and midwives on the day of insertion or 14 days post insertion lies to the right of −2%. Results In September and October 2015, we trained 60 CHEWs and a total of 60 nurses and midwives from 12 local government areas (LGAs) in Kaduna and 23 LGAs in Ondo. Recruitment took place between November 2015 and December 2016. Data analysis is being finalized, and results are expected in March 2018. Conclusions The strength of this study is having a standard care (nurse and midwife provision) group with which CHEW provision can be compared. The intervention builds on existing training and supervision procedures, which increases the sustainability and scalability of CHEW implant provision. Important limitations include the lack of randomization due to nurses and midwives in Nigeria working in separate types of health care facilities compared with CHEWs, and that providers self-assess their own practices. It is unfeasible to observe all procedures independently, and observation may change practice. Although providers will be trained to conduct implant removals, the study time will be too short to reach the sample size required to make noninferiority comparisons for removals. Trial Registration ClinicalTrials.gov NCT03088722; https://clinicaltrials.gov/ct2/show/NCT03088722 (Archived by WebCite at http://www.webcitation.org/6xIHImWvu) PMID:29500162

Freeze-dried, cross-linked bovine type I collagen: analysis of properties.

PubMed

Hyder, P R; Dowell, P; Singh, G; Dolby, A E

1992-03-01

This study was undertaken to assess the physical and biological properties of freeze-dried cross-linked bovine type I collagen and to assess its potential for use in the guided tissue regeneration method of treatment of periodontal disease in human adult subjects. The modulus of elasticity, swelling ratio, and biodegradation rate were investigated. The collagen sponge was implanted subdermally into Sprague-Dawley rats and a histological study carried out at 2, 7, 21, 35, and 49 days post implantation. Growth of human gingival and periodontal ligament derived fibroblasts on collagen sponge was assessed, as well as the effect of bovine collagen supernatants upon gingival and periodontal fibroblast cultures. The physical properties of the collagen sponge were consistent with good handling qualities and, therefore, it was appropriate for use at a surgical site. The histological study demonstrated a reduction in thickness of the collagen at 21 days; at 35 days there was a hazy appearance of the collagen remnants; and at 49 days the graft material had been completely replaced with fibrous tissues. The in vitro response of human gingival and periodontal fibroblasts to bovine collagen showed that, after 21 days, confluent fibroblast growth was observed around and underneath the sponge. The effect of bovine collagen supernatants upon fibroblasts demonstrated an apparent proliferative effect of the supernatant with both gingival and periodontal ligament fibroblasts. However, the non-parametric Friedman test revealed no significant differences between dilutions or time points. The overall findings provide encouraging evidence of the safety of freeze-dried cross-linked bovine collagen sponge in the surgical treatment of periodontal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

On the horizon: new options for contraception.

PubMed

Reifsnider, E

1997-01-01

Future contraceptives include refinements of existing contraceptives and totally new methods. New formulations of oral contraceptives, subdermal hormonal implants, injectable hormones, vaginal spermicides, and intrauterine devices (IUDs) are being tested around the world. New methods that are not yet available include the use of vaginal preparations containing sperm-immobilizing agents, gonadotrophin releasing hormone agonists and antagonists, vaccines against ova and sperm, and endogenous hormones. Male contraceptive methods use hormones to suppress testosterone and vaccines to immobilize sperm. The availability of all future contraceptives is dependent on ample funds for research, development, and testing, and such funds are in jeopardy.

Compensating for Tissue Changes in an Ultrasonic Power Link for Implanted Medical Devices.

PubMed

Vihvelin, Hugo; Leadbetter, Jeff; Bance, Manohar; Brown, Jeremy A; Adamson, Robert B A

2016-04-01

Ultrasonic power transfer using piezoelectric devices is a promising wireless power transfer technology for biomedical implants. However, for sub-dermal implants where the separation between the transmitter and receiver is on the order of several acoustic wavelengths, the ultrasonic power transfer efficiency (PTE) is highly sensitive to the distance between the transmitter and receiver. This sensitivity can cause large swings in efficiency and presents a serious limitation on battery life and overall performance. A practical ultrasonic transcutaneous energy transfer (UTET) system design must accommodate different implant depths and unpredictable acoustic changes caused by tissue growth, hydration, ambient temperature, and movement. This paper describes a method used to compensate for acoustic separation distance by varying the transmit (Tx) frequency in a UTET system. In a benchtop UTET system we experimentally show that without compensation, power transfer efficiency can range from 9% to 25% as a 5 mm porcine tissue sample is manipulated to simulate in situ implant conditions. Using an active frequency compensation method, we show that the power transfer efficiency can be kept uniformly high, ranging from 20% to 27%. The frequency compensation strategy we propose is low-power, non-invasive, and uses only transmit-side measurements, making it suitable for active implanted medical device applications.

Metabolic effects of the contraceptive skin patch and subdermal contraceptive implant in Mexican women: A prospective study

PubMed Central

2014-01-01

Background The contraceptive skin patch (CSP) accepted by the U.S. FDA in 2001 includes ethinylestradiol and norelgestromine, whereas the subdermal contraceptive implant (SCI) has etonogestrel and is also approved by the FDA. In Mexico, both are now widely used for contraception but their effects on Mexican population are unknown. The objective of the study was to evaluate if these treatments induce metabolic changes in a sample of indigenous and mestizo Mexican women. Methods An observational, prospective, longitudinal, non-randomized study of women between 18 and 35 years of age assigned to CSP or SCI. We performed several laboratory tests: clinical chemistry, lipid profile, and liver and thyroid function tests. Also, serum levels of insulin, C-peptide, IGF-1, leptin, adiponectin, and C reactive protein were assayed. Results Sixty-two women were enrolled, 25 used CSP (0 indigenous; 25 mestizos) and 37 used SCI (18 indigenous; 19 mestizos). Clinical symptoms were relatively more frequent in the SCI group. Thirty-four contraceptive users gained weight without other clinical significant changes. After 4 months of treatment, significant changes were found in some biochemical parameters in both treatment groups. Most were clinically irrelevant. Interestingly, the percentage of users with an abnormal atherogenic index diminished from 75% to 41.6% after follow-up. Conclusions The CSP slightly modified the metabolic variables. Most changes were nonsignificant, whereas for SCI users changes were more evident and perhaps beneficial. Results of this attempt to evaluate the effects of contraceptives in mestizo and native-American populations show that clinical symptoms are frequent in Mexican users of CSP and SCI. Although these medications may affect some metabolic variables, these changes seem clinically irrelevant. Induction of abnormalities in other physiological pathways cannot be ruled out. PMID:24767248

Use of a single implant of elcometrine (ST-1435), a nonorally active progestin, as a long acting contraceptive for postpartum nursing women.

PubMed

Coutinho, E M; Athayde, C; Dantas, C; Hirsch, C; Barbosa, I

1999-02-01

Because of its unique features, the contraceptive effectiveness and tolerance during breast-feeding of 16-methylene-17 alpha-acetoxy-19-nor-4-pregnene-3,20-dione (elcometrine), delivered within a single subdermal capsule of medical grade polydimethylsiloxane, was investigated. Unlike other progestational steroids, elcometrine has no affinity for androgen and estrogen receptors and is inactive by the oral route. A total of 66 breast-feeding women receiving elcometrine by the subdermal route were enrolled in the study, and 69 women who elected to use Copper-T380 intrauterine devices (IUD) served as control subjects. The women and their infants were observed until the end of the first postpartum year. There were no significant differences in growth and development measurements among the infants in the elcometrine and control groups. The percentage of infants continuing to breast-feed at 3 and 6 months was significantly higher in the elcometrine group. There were no significant differences between the concentration of elcometrine in the mother's blood and milk. At 75 days, blood levels of elcometrine in the infants were near the undetectable and were significantly lower than the levels in maternal blood or milk (p < 0.01). In 15 of 25 infants, blood levels of elcometrine were at the limit of assay sensitivity or undetectable. Two pregnancies occurred in women using IUD, whereas none occurred in those using implants. There were menstrual bleeding irregularities in both groups. A single elcometrine capsule placed subcutaneously at 6-monthly intervals appears to be an effective method of contraception for lactating women and results in blood concentrations of nursing infants at or near undetectable levels.

The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience.

PubMed

Graesslin, Olivier; Korver, Tjeerd

2008-06-01

To evaluate the contraceptive efficacy of the etonogestrel-releasing implant Implanon as assessed in international studies and during nine years of marketing experience. The analysis included 11 international studies and data collected during nine years of marketing experience (1998--2007). Seven of these studies were noncomparative; the four other studies included the 6-rod levonorgestrel implant system or an intrauterine device as a comparator. All studies except one were of at least two years in duration, and all had contraceptive efficacy as the objective. Market data were provided unsolicited to Organon, part of Schering Plough. The integrated efficacy analysis included 923 non-breastfeeding women who were exposed to the implant for 24,100 cycles. No in-treatment or pretreatment pregnancies were reported. Fifty posttreatment pregnancies were reported, six of which occurred within 14 days of implant removal, indicating that fertility had quickly returned. Over a nine-year marketing period an overall pregnancy rate of 0.049 per 100 implants sold (estimated Pearl Index = 0.031 based on all pregnancies reported) was calculated. When only counting contraceptive method failures the pregnancy rate amounts to 0.010 per 100 implants sold (estimated Pearl Index = 0.006). Implanon is a highly effective and quickly reversible subdermal method of long-acting hormonal contraception for women. Typical use of this implant achieves a contraceptive protection exceeding 99%.

Knowledge and Acceptability of Long-Acting Reversible Contraception Among Adolescent Women Receiving School-Based Primary Care Services.

PubMed

Hoopes, Andrea J; Ahrens, Kym R; Gilmore, Kelly; Cady, Janet; Haaland, Wren L; Amies Oelschlager, Anne-Marie; Prager, Sarah

2016-07-01

A key strategy to reduce unintended adolescent pregnancies is to expand access to long-acting reversible contraceptive (LARC) methods, including intrauterine devices and subdermal contraceptive implants. LARC services can be provided to adolescents in school-based health and other primary care settings, yet limited knowledge and negative attitudes about LARC methods may influence adolescents' utilization of these methods. This study aimed to evaluate correlates of knowledge and acceptability of LARC methods among adolescent women at a school-based health center (SBHC). In this cross-sectional study, female patients receiving care at 2 SBHCs in Seattle, Washington completed an electronic survey about sexual and reproductive health. Primary outcomes were (1) LARC knowledge as measured by percentage correct of 10 true-false questions and (2) LARC acceptability as measured by participants reporting either liking the idea of having an intrauterine device (IUD)/subdermal implant or currently using one. A total of 102 students diverse in race/ethnicity and socioeconomic backgrounds completed the survey (mean age 16.2 years, range 14.4-19.1 years). Approximately half reported a lifetime history of vaginal sex. Greater LARC knowledge was associated with white race (regression coefficient [coef] = 26.8; 95% CI 13.3-40.4; P < .001), history of vaginal intercourse (coef = 29.9; 95% CI 17.1-42.7; P < .001), and current/prior LARC use (coef = 22.8; 95% CI 6.5-40.0; P = .007). Older age was associated with lower IUD acceptability (odds ratio = 0.53, 95% CI 0.30-0.94; P = .029) while history of intercourse was associated with greater implant acceptability (odds ratio 5.66, 95% CI 1.46-22.0; P = .012). Adolescent women in this SBHC setting had variable knowledge and acceptability of LARC. A history of vaginal intercourse was the strongest predictor of LARC acceptability. Our findings suggest a need for LARC counseling and education strategies, particularly for young women from diverse cultural backgrounds and those with less sexual experience. © The Author(s) 2016.

Knowledge and Acceptability of Long-Acting Reversible Contraception Among Adolescent Women Receiving School-Based Primary Care Services

PubMed Central

Hoopes, Andrea J.; Ahrens, Kym R.; Gilmore, Kelly; Cady, Janet; Haaland, Wren L.; Amies Oelschlager, Anne-Marie; Prager, Sarah

2016-01-01

Background: A key strategy to reduce unintended adolescent pregnancies is to expand access to long-acting reversible contraceptive (LARC) methods, including intrauterine devices and subdermal contraceptive implants. LARC services can be provided to adolescents in school-based health and other primary care settings, yet limited knowledge and negative attitudes about LARC methods may influence adolescents’ utilization of these methods. This study aimed to evaluate correlates of knowledge and acceptability of LARC methods among adolescent women at a school-based health center (SBHC). Methods: In this cross-sectional study, female patients receiving care at 2 SBHCs in Seattle, Washington completed an electronic survey about sexual and reproductive health. Primary outcomes were (1) LARC knowledge as measured by percentage correct of 10 true-false questions and (2) LARC acceptability as measured by participants reporting either liking the idea of having an intrauterine device (IUD)/subdermal implant or currently using one. Results: A total of 102 students diverse in race/ethnicity and socioeconomic backgrounds completed the survey (mean age 16.2 years, range 14.4-19.1 years). Approximately half reported a lifetime history of vaginal sex. Greater LARC knowledge was associated with white race (regression coefficient [coef] = 26.8; 95% CI 13.3-40.4; P < .001), history of vaginal intercourse (coef = 29.9; 95% CI 17.1-42.7; P < .001), and current/prior LARC use (coef = 22.8; 95% CI 6.5-40.0; P = .007). Older age was associated with lower IUD acceptability (odds ratio = 0.53, 95% CI 0.30-0.94; P = .029) while history of intercourse was associated with greater implant acceptability (odds ratio 5.66, 95% CI 1.46-22.0; P = .012). Discussion: Adolescent women in this SBHC setting had variable knowledge and acceptability of LARC. A history of vaginal intercourse was the strongest predictor of LARC acceptability. Our findings suggest a need for LARC counseling and education strategies, particularly for young women from diverse cultural backgrounds and those with less sexual experience. PMID:27067583

Unscheduled vaginal bleeding with progestin-only contraceptive use.

PubMed

Zigler, Rachel E; McNicholas, Colleen

2017-05-01

Nearly 20% of women using contraception are using progestin-only contraception, including progestin-only pills, depot-medroxyprogesterone acetate, subdermal etonogestrel implants, and levonorgestrel intrauterine devices. This number will continue to grow with the increased provision of long-acting reversible contraception. Although overall satisfaction among women using progestin-only contraception is high, dissatisfaction and discontinuation may be associated with unscheduled bleeding and spotting. The exact etiology of irregular bleeding associated with progestin-containing contraceptives is not completely understood, yet several mechanisms have been suggested. Several therapies targeting these mechanisms have been evaluated with mixed results. This paper will review the physiology and management of unscheduled bleeding with progestin-containing contraceptives. Copyright © 2016 Elsevier Inc. All rights reserved.

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant

PubMed Central

Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine®, which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed. PMID:28546740

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant.

PubMed

Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine ® , which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed.

Monitoring of urea and potassium by reverse iontophoresis in vitro.

PubMed

Wascotte, Valentine; Delgado-Charro, M Begoña; Rozet, Eric; Wallemacq, Pierre; Hubert, Philippe; Guy, Richard H; Préat, Véronique

2007-06-01

Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined. In vitro experiments were performed to test (a) a series of subdermal urea and potassium concentrations typical of the pathophysiologic range, and (b) a decreasing profile of urea and potassium subdermal concentrations to mimic those which are observed during hemodialysis. (a) After 60-120 min of iontophoresis, linear relationships (p < 0.05) were established between both urea and potassium fluxes and their respective subdermal concentrations. The determination coefficients were above 0.9 after 1 h of current passage using sodium as an internal standard. (b) Reverse iontophoretic fluxes of urea and K(+) closely paralleled the decay of the respective concentrations in the subdermal compartment, as would occur during a hemodialysis session. These in vitro experiments demonstrate that urea and potassium can be quantitatively and proportionately extracted by reverse iontophoresis, even when the subdermal concentrations of the analytes are varying with time. These results suggest the non-invasive monitoring of urea and potassium to diagnose renal failure and during hemodialysis is feasible, and that in vivo measurements are warranted.

Effect of osteoporosis on fixation of osseointegrated implants in rats.

PubMed

Li, Yunfeng; He, Sheng; Hua, Yunwei; Hu, Jing

2017-11-01

The effect of osteoporosis on implant osseointegration has been widely investigated, whereas osteoporosis may also newly occur in patient with previously osseointegrated implant. This study was designed to investigate the effect of osteoporosis on implant fixation in rats after successful osseointegration had been obtained. Seventy female Sprague-Dawley rats were included, and each animal received two titanium implants in the distal metaphysis of femur bilaterally. Eight weeks later, ten rats were sacrificed to confirm the establishment of implant osseointegration. All left rats were randomly subjected to bilateral ovariectomy (OVX) or sham operation. Three, six, and twelve weeks later, implant osseointegration, peri-implant bone tissue, and biomechanical properties of implant were analyzed. Right femurs with implants were used for micro-CT and histological analysis, and left femurs with implants were used for biomechanical test. Micro-CT, histology, and biomechanical test confirmed the destructive effect of OVX on previously osseointegrated implant in rats; when compared to sham-operated rats, peri-implant bone volume, trabecular architecture, bone-to-implant contact ratio, as well as biomechanical parameters decreased progressively within 12 weeks. Results also indicated that the effect of OVX on undisturbed bone (proximal tibiae) was much stronger than that on peri-implant bone. Osteoporosis produced a progressive negative effect on previously osseointegrated implant in distal femora of rats during 12 weeks. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2426-2432, 2017. © 2016 Wiley Periodicals, Inc.

Patients' perspectives about why they have their contraceptive Implanon NXT device removed early.

PubMed

Flore, Meike; Chen, Xiaoshuang Lilly; Bonney, Andrew; Mullan, Judy; Dijkmans-Hadley, Bridget; Hodgkins, Adam; Evans, Gina; Frew, Haley; Lloyd, Gail

2016-10-01

Women with long-acting, reversible contraceptive devices inserted may choose to remove them prior to their planned expiry dates. The objective of this study was to explore Australian women's experiences with the etonogestrel subdermal contraceptive implant (Implanon NXT) and why they had it removed early. Semi-structured interviews were conducted with 18 women between June 2013 and January 2014. Transcriptions of the audio-taped interviews were analysed using a constant comparative analysis framework. Two core themes of participants' responses that were identified in this study were influences on choice of contraception, which included convenience and information sources; and influences on removal of contraception, which included side effects and their negative impacts on relationships and financial costs. This study highlights that women's experiences with side effects contribute to the early removal of long-acting contraceptive devices such as Implanon NXT. This study emphasises the importance of general practitioners (GPs) in providing comprehensive information about the benefits and potential side effects associated with using these implants.

Young women's attitudes toward injectable and implantable contraceptives.

PubMed

Gold, M A; Coupey, S M

1998-02-01

To assess the potential acceptability of implantable and injectable contraceptive characteristics by young women of diverse ethnic and educational backgrounds. A cross-sectional self-administered survey. The waiting room of three clinical sites: an elite women's college health service, a coeducational state university health service, and an inner city hospital-based adolescent clinic. 328 young women awaiting medical care in one of three clinical sites, aged 13 to 21 years (85% 18-21 years); ethnic distribution differed significantly by site. The majority (83%) were sexually active, and of those who were sexually experienced, 25% had been pregnant. A 47-item questionnaire examining attitudes toward characteristics of injectable and implantable contraceptive methods, menstrual, sexual, and gynecologic history. Sixty-two percent of the sample agreed that they would get an injectable method. There was little variation in agreement to get an injectable method by sexual or pregnancy history. Fewer subjects (24%) agreed that they would like to get subdermal implants and agreement to get an implantable method of contraception did not vary by sexual history; however, ever-pregnant young women (33%) were significantly more likely to agree to implants than never-pregnant subjects (21%; chi2, 4.109; p = 0.04). Seventy-four percent of subjects said they would stop using a contraceptive that caused irregular menses, whereas 65% would stop using a method that caused amenorrhea. An injectable contraceptive method has universal appeal across ethnic, educational, and age categories, whereas implants are less appealing. Irregular bleeding and amenorrhea are poorly perceived side effects of long-acting contraceptives.

Near-Infrared Irradiation Increases Length of Axial Pattern Flap Survival in Rats.

PubMed

Yasunaga, Yoshichika; Matsuo, Kiyoshi; Tanaka, Yohei; Yuzuriha, Shunsuke

2017-01-01

Objective: We previously reported that near-infrared irradiation nonthermally induces long-lasting vasodilation of the subdermal plexus by causing apoptosis of vascular smooth muscle cells. To clarify the possible application of near-infrared irradiation to prevent skin flap necrosis, we evaluated the length of axial pattern flap survival in rats by near-infrared irradiation. Methods: A bilaterally symmetric island skin flap was elevated under the panniculus carnosus on the rat dorsum. Half of the flap was subjected to near-infrared irradiation just before flap elevation with a device that simulates solar radiation, which has a specialized contact cooling apparatus to avoid thermal effects. The length of flap survival of the near-infrared irradiated side was measured 7 days after flap elevation and compared with the nonirradiated side. Results: The irradiated side showed elongation of flap survival compared with the nonirradiated side (73.3 ± 11.7 mm vs 67.3 ± 14.9 mm, respectively, P = .03). Conclusions: Near-infrared irradiation increases the survival length of axial pattern flaps in rats.

Subdermal liposuction.

PubMed

Gasperoni, C; Salgarello, M; Emiliozzi, P; Gargani, G

1990-01-01

Liposuction is a widely used technique today and indications are that it is becoming even more popular due to new technical refinements. The use of cannulae with a smaller diameter allows suction of the fat immediately under the dermis. The cannula we use to perform this new kind of fat suction is straight and has an external diameter of less than 2 mm. This cannula, the so-called Mercedes cannula, has a bullet tip and a three-hole head. Moreover, the holes are not round but are slit-shaped and oriented in the same plane at 120 degrees. This cannula is specifically designed to produce less trauma. The cannula with one downward-facing orifice is not suitable for suction of the subdermal layer and an upward-facing orifice would be too traumatic. The advantage of this new technique, apart from the possibility of treating patients with very slight adiposity, is to allow an effective skin retraction. When a large amount of fat has already been aspirated, residual deformities can occur. These skin irregularities represent the lack of an effective cutaneous retraction mostly due to the permanence of the subdermal fat. In fact, the presence of a thick subdermal adipose layer decreases the possibility of skin retraction. Therefore, indications for liposuction of the subdermal fat are mainly the slight adiposities and the remnant deformities of a previous liposuction operation. Moreover, this technique is applied to every lipoplasty whenever better skin retraction is needed.

Experience of Thai women in Bangkok with Norplant-2 implants.

PubMed

Chompootaweep, S; Kochagarn, E; Tang-Usaha, J; Theppitaksak, B; Dusitsin, N

1998-10-01

A prospective study of the Norplant-2 contraceptive subdermal implant system was conducted in Bangkok, Thailand. The objective of the study was to evaluate the efficacy, adverse effects, and overall acceptability of Norplant-2 implants. A total of 140 women were enrolled in a 3-year clinical trial. The mean age was 29 years. Of all the acceptors, 70% had completed primary school. The continuation rates at years 1, 2, and 3 were, respectively, 94%, 89%, and 83%. No accidental pregnancies occurred throughout the 3 years of use in this study. Personal reasons were the leading cause for termination of Norplant-2 implant use. The 3-year cumulative termination rate for personal reasons was 7.2%. These personal reasons were divorce, husband having vasectomy, and moving away from the study area. The other leading cause for termination was medical reasons; acne, headache, and pain at the implant site were the complaints. The termination rate for medical reasons in year 3 of the study was 4.6%. Prolonged menstrual flow was the other main reason for termination. The 3-year cumulative termination rate for menstrual irregularities was 3.8%. In this study, the cumulative termination for planned pregnancy at the end of the year 3 was only 1.6%. The incidence of difficult removals was 8%. Breakage of the rods on removal was encountered in the majority of these cases. The study findings presented suggest that the Norplant-2 implants are highly effective with high continuation rates. The Norplant-2 system could become another choice of long acting reversible contraception for Thai women.

Uptake and early removals of Implanon NXT in South Africa: Perceptions and attitudes of healthcare workers

PubMed

Adeagbo, O; Mullick, S; Pillay, D; Chersich, M; Morroni, C; Naidoo, N; Pleaner, M; Rees, H

2017-10-01

Background. The South African (SA) government introduced Implanon NXT, a long-acting subdermal contraceptive implant, in 2014 to expand contraceptive choice. Following an initial high uptake, its use declined considerably amid reports of early removals and frequent side-effects. We examine providers’ perceptions of training and attitudes towards Implanon NXT, as well as their views on the causes of early removals and the impact on the implant service. Objective. To assess healthcare providers’ perceptions and attitudes towards implant services in SA. Methods. In-depth interviews were conducted with eight nurses providing implant services in public facilities in Gauteng and North West Province. Emerging themes were identified, manually coded and thematically analysed following an interpretivism approach. Results. Nurses lacked confidence in providing implant services effectively, particularly removals, which they ascribed to the brief, cascade-type training received. Nurses generally held negative views towards the method. They also reported that side-effects are the most common reason for early removals – particularly irregular bleeding – and that men often do not support their partners who use the method. Lastly, it was found that providers require guidance on counselling regarding the method and standardised guidelines on the management of side-effects. Conclusion. Retraining and support of providers are needed to address competency gaps and negative attitudes towards the method. Assessment of providers’ readiness to perform removal procedures is also important. Finally, effective plans are necessary to improve implant continuation rates, especially among women whose partners are unsupportive. Creative Commons Attribution - NonCommercial Works License (CC BY-NC 4.0)

Probuphine® (buprenorphine implant): a promising candidate in opioid dependence

PubMed Central

Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

2016-01-01

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits. PMID:28348732

Probuphine® (buprenorphine implant): a promising candidate in opioid dependence.

PubMed

Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

2017-03-01

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits.

[External periareolar incision for subdermal mastectomy in men with gynecomastia].

PubMed

Montiel-Jarquín, Alvaro; Reyes-Páramo, Pedro; Ramos-Alvarez, Gloria; López-Colombo, Aurelio; Tinajero-Esquivel, Magdalena; Ruiz-León, Betzabé

2007-01-01

Gynecomastia describes a benign increase of the mammary gland in men. When medical treatment fails, symptoms and psychological alterations persist. Subdermal mastectomy is the definitive treatment and can be achieved by different incisions, each with potential complications. We undertook this study to present clinical characteristics of 11 patients with gynecomastia and the results obtained with subdermal mastectomy by means of external periareolar incision. A descriptive cohort study in male patients with gynecomastia was carried out in a third-level medical care hospital. Patients were treated with subdermal mastectomy by means of external periareolar incision. There were 11 male patients with an average age of 19 years (range: 11-60 years), 3 patients (27.2%) with bilateral gynecomastia and 8 patients (72.7%) with unilateral gynecomastia. Average time of evolution was 22 months (range: 16-48 months), 9 patients (81.8%) reported pain, 11 patients (100%) reported psychological alterations with cutaneous alteration, 11 patients (100%) had normal secondary sexual characteristics, 1 patient (9%) had supernumerary nipple development, and 11 patients (100%) had well-defined lesions. According to Simon's classification: seven patients (63.6%) were classified as grade 1, three patients (27.2%) as grade 2 and one patient (9.09%) as grade 3. Each patient had a subdermal mastectomy with external periareolar incision, 11 patients (100%) had a histopathological report of gynecomastia; 1 patient (9.09%) displayed keloid healing and none displayed complications inherent to the surgical procedure. Mastectomy by means of external periareolar incision is useful in the treatment of gynecomastia.

Antibacterial effect of royal jelly for preservation of implant-related spinal infection in rat.

PubMed

Gunaldi, Omur; Daglioglu, Yusuf Kenan; Tugcu, Bekir; Kizilyildirim, Suna; Postalci, Lutfi; Ofluoglu, Ender; Koksal, Fatih

2014-01-01

Implant-related infections are still a significant problem in spinal surgical procedures. Many drugs and methods have been tried to prevent implant-related infections. Our objective in this study was to evaluate whether royal jelly, which was found to hinder the growth of MRSA, has any preventive role in the prognosis of an infection in rats in an implant-related infection model. Rats were divided into 3 groups of eight rats. Group-1 consisted of rats that underwent only a spinal implant, group-2 included those rats that were inoculated bacteria together with a spinal implant and group-3 was administered royal jelly in addition to a spinal implant and infection. The amount of bacteria that grew in vertebral columns and implants was more in Group-2 than in Group-3, which meant that the number of bacteria colonies that grew was more quantitatively. This difference was found to be statistically significant in vertebral columns, but not in implants. Royal jelly could not fully prevent the MRSA infection in this model, but decreased the severity of infection noticeably. More objective and promising results may be obtained if royal jelly can be used at regular intervals in a different model to be designed with respect to implant-related infections.

MALL liposuction: the natural evolution of subdermal superficial liposuction.

PubMed

Gasperoni, C; Salgarello, M

1994-01-01

Subdermal superficial liposuction, first presented by the authors at the ISAPS Congress at Zurich in 1989, is performed with thin three-hole Mercedes cannulas (diameter ranges from 1.8 to 2 mm) to treat small and secondary adiposities and to allow better skin retraction. Suction of the subdermal layer of fat reduces the thickness and consistency of the superficial fat and enhances the possibility of skin retraction. In cases where there is a large adiposity of the abdomen, arms, or inner thighs, there is a conspicuous volume of fat whose weight tends to overstretch and to carry the overlying skin downward. In these cases we need to reduce the large fat volume to permit effective skin retraction. Therefore, we apply the principles of traditional liposuction with those of subdermal superficial liposuction to aspirate large amounts of fat from all the adipose layers. We call this technique Massive All Layer Liposuction (MALL). The amount of skin shrinkage after this "defatting" procedure is remarkable and the clinical results are very good. The MALL technique can be applied to other areas as well. In our experience this new liposuction technique has dramatically reduced the indications of abdominoplasties and dermolipectomies of inner thighs and arms.

People’s Republic of China Scientific Abstracts, Number 184

DTIC Science & Technology

1978-01-23

Sciences. 29 AUTHOR: CHANG Hsiao-hsien [1728 2400 0341] ORG: Niu-chuang Commune Health Clinic, Kaifeng, Honan TITLE: "Subdermal Petechial Hemorrhage...dysentery, and after 3 days the symptoms reappeared, with petechial hemorrhage spreading to axillary fossae and inner thighs. Patient had had many...sulfa drugs before with no adverse reaction, which confirmed that subdermal petechial hemorrhage was caused by oral administration of long-acting

Seroma Formation in Rat Latissimus Dorsi Resection in the Presence of Biologics: The Role of Quilting.

PubMed

Hurwitz, Zachary M; Ignotz, Ronald A; Rowin, Craig; Freniere, Brian B; Lalikos, Janice F; Dunn, Raymond M

2015-09-01

Seroma formation is a well-recognized complication associated with many operative procedures. Despite its ubiquity, a lack of definitive scientific understanding of the etiology, natural history, and biochemistry of seromas remains. We endeavored to create and examine seromas in a rat model in the setting of commonly used biologic implants and to examine the role of quilting sutures/mechanical fixation in mitigating seroma development. Female Sprague-Dawley rats were assigned to either Quilting or Nonquilting groups then subdivided into one of 3 porcine dermal implant groups (Permacol Surgical Implant, Strattice Reconstructive Tissue Matrix, or XCM Biologic Tissue Matrix) or control group. A 5-cm midline back incision was made, the skin reflected and the latissimus dorsi muscle resected bilaterally. Implants were sutured into the surgical bed using a running suture. The skin of nonquilted rats was closed with a running subcuticular suture. Quilted rats underwent placement of absorbable quilting sutures spaced 2 cm apart between the skin and underlying implant or muscle before skin closure. Postoperatively, rats were monitored for seroma formation with fluid aspirated as needed. At 28 or 90 days, rats were euthanized. Seroma and implants were examined grossly and under light microscopy. Of nonquilted rats, 42/54 (78%) developed seromas compared with 19/46 (41%) of quilted rats (P < 0.05), defined by bursa cavity present at necropsy. When a biologic implant was present, 28/35 (80%) of nonquilted rats developed seromas compared with 12/33 (36%) of quilted rats (P < 0.05). In the control group, 14/19 (74%) of nonquilted rats developed seromas compared with 7/13 (54%) of quilted rats. This difference was not statistically significant. Bursa presence was confirmed histologically in all cases, with no difference in bursa character seen between groups. This study confirms a reliable rat model of seroma formation, with most of the rats exhibiting at least subclinical seromas. There was no difference in seroma formation rate in the presence of biologic implants, and no differences in bursa character between implants. Mechanical fixation with quilting sutures decreased seroma rate significantly in all subgroups. All rats with seromas at necropsy had histological evidence of a bursa with no difference in appearance between groups.

Skin microdialysis coupled with laser speckle contrast imaging to assess microvascular reactivity.

PubMed

Cracowski, J L; Gaillard-Bigot, F; Cracowski, C; Roustit, M; Millet, C

2011-11-01

Laser speckle contrast imaging (LSCI) can be used to assess real-time responses of skin microcirculation to pharmacological interventions. The main objective of this study was to determine whether intradermal or subdermal microdialysis fiber insertion, coupled with skin flux recording using LSCI, can be used to assess baseline cutaneous flux and the post-occlusive reactive hyperemic response. The microdialysis sites were compared to control area without microdialysis fibers. One dermal and two subdermal microdialysis fibers were randomly inserted in the right forearm skin of six healthy volunteers. We performed consecutively tests of post-occlusive hyperemia, infusion of 29 mM sodium nitroprusside (SNP), local thermal hyperemia at 43°C and a second 29 mM SNP infusion at the end of the experiment. Two hours after fiber insertion, cutaneous vascular conductances (CVC) at the subdermal fiber sites were not different from their respective control regions of interest, while at the dermal site CVC remained higher (0.48+/-0.15 versus 0.37+/-0.1 PU.mm Hg(-1), P=0.003). The peak CVC and area under the curve observed during post-occlusive reactive hyperemia were similar at all fiber sites and their respective controls. We observed a similar increase in CVC using 29 mM SNP infusion, 40 min local heating at 43°C, and their combination. Finally, physiological and pharmacological responses of the subdermal sites were reproducible in terms of amplitude, whether expressed as raw CVC or as % CVCmax. We showed that studying skin microvascular physiological or pharmacological responses using inserted subdermal microdialysis fibers coupled with LSCI is feasible and reproducible, and provides two-dimensional information. This technique will be useful for future mechanistic studies of skin microcirculation. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of tensile strength among simple interrupted, cruciate, intradermal, and subdermal suture patterns for incision closure in ex vivo canine skin specimens.

PubMed

Zellner, Eric M; Hedlund, Cheryl S; Kraus, Karl H; Burton, Andrew F; Kieves, Nina R

2016-06-15

OBJECTIVE To compare suture placement time, tension at skin separation and suture line failure, and mode of failure among 4 suture patterns. DESIGN Randomized trial. SAMPLE 60 skin specimens from the pelvic limbs of 30 purpose-bred Beagles. PROCEDURES Skin specimens were harvested within 2 hours after euthanasia and tested within 6 hours after harvest. An 8-cm incision was made in each specimen and sutured with 1 of 4 randomly assigned suture patterns (simple interrupted, cruciate, intradermal, or subdermal). Suture placement time and percentage of skin apposition were evaluated. Specimens were mounted in a calibrated material testing machine and distracted until suture line failure. Tensile strength at skin-edge separation and suture-line failure and mode of failure were compared among the 4 patterns. RESULTS Mean suture placement time for the cruciate pattern was significantly less than that for other patterns. Percentage of skin apposition did not differ among the 4 patterns. Mean tensile strength at skin-edge separation and suture-line failure for the simple interrupted and cruciate patterns were significantly higher than those for the intradermal and subdermal patterns. Mean tensile strength at skin-edge separation and suture-line failure did not differ significantly between the intradermal and subdermal patterns or the simple interrupted and cruciate patterns. The primary mode of failure for the simple interrupted pattern was suture breakage, whereas that for the cruciate, intradermal, and subdermal patterns was tissue failure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested external skin sutures may be preferred for closure of incisions under tension to reduce risk of dehiscence.

Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder.

PubMed

Carter, John A; Dammerman, Ryan; Frost, Michael

2017-08-01

Subdermal implantable buprenorphine (BSI) was recently approved to treat opioid use disorder (OUD) in clinically-stable adults. In the pivotal clinical trial, BSI was associated with a higher proportion of completely-abstinent patients (85.7% vs 71.9%; p = .03) vs sublingual buprenorphine (SL-BPN). Elsewhere, relapse to illicit drug use is associated with diminished treatment outcomes and increased costs. This study evaluated the cost-effectiveness of BSI vs SL-BPN from a US societal perspective. A Markov model simulated BSI and SL-BPN cohorts (clinically-stable adults) transiting through four mutually-exclusive health states for 12 months. Cohorts accumulated direct medical costs from drug acquisition/administration; treatment-diversion/abuse; newly-acquired hepatitis-C; emergency room, hospital, and rehabilitation services; and pediatric poisonings. Non-medical costs of criminality, lost wages/work-productivity, and out-of-pocket expenses were also included. Transition probabilities to a relapsed state were derived from the aforementioned trial. Other transition probabilities, costs, and health-state utilities were derived from observational studies and adjusted for trial characteristics. Outcomes included incremental cost per quality-adjusted-life-year (QALY) gained and incremental net-monetary-benefit (INMB). Uncertainty was assessed by univariate and probabilistic sensitivity analysis (PSA). BSI was associated with lower total costs (-$4,386), more QALYs (+0.031), and favorable INMB at all willingness-to-pay (WTP) thresholds considered. Higher drug acquisition costs for BSI (+$6,492) were outpaced, primarily by reductions in emergency room/hospital utilization (-$8,040) and criminality (-$1,212). BSI was cost-effective in 89% of PSA model replicates, and had a significantly higher NMB at $50,000/QALY ($20,783 vs $15,007; p < .05). BSI was preferred over SL-BPN from a health-economic perspective for treatment of OUD in clinically-stable adults. These findings should be interpreted carefully, due to some relationships having been modeled from inputs derived from multiple sources, and would benefit from comparison with outcomes from studies that employ administrative claims data or a naturalistic comparative design.

Freezing of Rat Tibiae at -20°C Does Not Affect the Mechanical Properties of Intramedullary Bone/Implant-Interface: Brief Report

PubMed Central

Diefenbeck, Michael; Mückley, Thomas; Zankovych, Sergiy; Bossert, Jörg; Jandt, Klaus D; Schrader, Christian; Schmidt, Jürgen; Finger, Ulrich; Faucon, Mathilde

2011-01-01

Background: The effects of freezing-thawing cycles on intramedullary bone-implant interfaces have been studied in a rat model in mechanical pull-out tests. Implants: Twenty TiAl6V4 rods (Ø 0.8 mm, length 10 mm) implanted in rat tibiae Methods: 10 rats underwent bilateral tibial implantation of titanium rods. At eight weeks, the animals were sacrificed and tibiae harvested for biomechanical testing. Eight tibiae were frozen and stored at -20°C for 14 days, the remaining eight were evaluated immediately post-harvest. Pull-out tests were used to determine maximum force and interfacial shear strength. Results: There were no significant differences between fresh and those of the frozen-thawed group in maximum force or in interfacial shear strength. Conclusion: Frozen Storage of rat tibiae containing implants at -20° C has no effects on the biomechanical properties of Bone/ Implant interface. PMID:21760868

Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats.

PubMed Central

Hahn, Fletcher F; Guilmette, Raymond A; Hoover, Mark D

2002-01-01

In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues. We compared the tissue reactions in rats to the carcinogenicity of a tantalum metal (Ta), as a negative foreign-body control, and to a colloidal suspension of radioactive thorium dioxide ((232)Th), Thorotrast, as a positive radioactive control. DU was surgically implanted in the thigh muscles of male Wistar rats as four squares (2.5 x 2.5 x 1.5 mm or 5.0 x 5.0 x 1.5 mm) or four pellets (2.0 x 1.0 mm diameter) per rat. Ta was similarly implanted as four squares (5.0 x 5.0 x 1.1 mm) per rat. Thorotrast was injected at two sites in the thigh muscles of each rat. Control rats had only a surgical implantation procedure. Each treatment group included 50 rats. A connective tissue capsule formed around the metal implants, but not around the Thorotrast. Radiographs demonstrated corrosion of the DU implants shortly after implantation. At later times, rarifactions in the radiographic profiles correlated with proliferative tissue responses. After lifetime observation, the incidence of soft tissue sarcomas increased significantly around the 5.0 x 5.0 mm squares of DU and the positive control, Thorotrast. A slightly increased incidence occurred in rats implanted with the 2.5 x 2.5 mm DU squares and with 5.0 x 5.0 mm squares of Ta. No tumors were seen in rats with 2.0 x 1.0 mm diameter DU pellets or in the surgical controls. These results indicate that DU fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be detected with radiography in the muscles of rats. PMID:11781165

Rationale of subdermal superficial liposuction related to the anatomy of subcutaneous fat and the superficial fascial system.

PubMed

Gasperoni, C; Salgarello, M

1995-01-01

The liposuction technique has changed greatly over the years. In 1989, the authors presented subdermal superficial liposuction which treats the superficial fat layer and yields better skin retraction. With this technique the surgeon can treat thin adipose layers to obtain better results in more cases than the traditional liposuction technique. The technique can be used in cases with difficult skin adjustment and in secondary cases when "deep only" liposuction has been performed and there were residual adiposities. Subdermal superficial liposuction evolved so that one could obtain good skin retraction by performing massive liposuction of all the fat layers. The authors named this technique MALL (Massive All Layer Liposuction). The technique is applied in body areas where the fat layer is very thick and stretches the skin because of its volume and weight such as in the abdomen, posterior arms, and internal surface of the upper third of the thighs. MALL liposuction drastically reduces the indications for abdominoplasty and inner thigh and arm dermolipectomies. Knowledge of the anatomy of the subcutaneous fat and the superficial fascial system allows one to explain the subdermal superficial liposuction from an anatomical point of view, to perform a more rational and effective procedure, and to differentiate the technique depending on the area of the body.

Strontium coating by electrochemical deposition improves implant osseointegration in osteopenic models

PubMed Central

LIANG, YONGQIANG; LI, HAOYAN; XU, JIANG; LI, XIN; LI, XINCHANG; YAN, YUTING; QI, MENGCHUN; HU, MIN

2015-01-01

Osteopenia, a preclinical state of osteoporosis, restricts the application of adult orthodontic implant anchorage and tooth implantation. Strontium (Sr) is able to promote bone formation and inhibit bone absorption. The aim of the present study was to evaluate a new method for improving the success rate of dental implantation. In this study, an electrochemical deposition (ECD) method was used to prepare a Sr coating on a titanium implant. The coating composition was investigated by energy dispersive X-ray spectroscopy and X-ray diffraction, and the surface morphology of the coating was studied using scanning electron microscopy. A total of 24 Sprague-Dawley rats received bilateral ovariectomy (OVX) and an additional 12 rats underwent a sham surgery. All rats were then implanted in the bilateral tibiae with titanium mini-implants with or without a Sr coating. The results of histological examination and a fluorescence double labeling assay showed strong new bone formation with a wider zone between the double labels, a higher rate of bone mineralization and better osseointegration in the OVX rats that received Sr-coated implants compared with the OVX rats that received uncoated implants. The study indicates that Sr coatings are easily applied by an ECD method, and that Sr coatings have a promoting effect on implant osseointegration in animals with osteopenia. PMID:25452797

Use of subdermal contraceptive implants in a community-based family planning program. Experience after two years.

PubMed

Mittelmark, M B; Hansen, W B; Shiferaw, B; Bradham, D D

1995-10-01

In North Carolina, the Rutherford County Family Planning Council obtained funds from a special grant for levonorgestrel implants for women not eligible for medical assistance benefits. The Council approved the following approaches to promoting responsible sexual behavior and preventing unwanted pregnancy: creation of an interagency council to monitor the program, education in the schools on responsible sexual behavior, establishment of an information-sharing network for social service agencies, and expanded, low-cost or free family planning services. During 1992-1993, clinicians at the county health department and in private practices inserted implants in 287 women aged 13-37 living mainly in Rutherford County but also in McDowell and Polk counties. A survey was also conducted in the public high school to obtain self-assessment and information about family planning from female adolescents. Age distribution of the acceptors of the contraceptive implants was 40% for 13-19 year olds (the initiative's target group), 34% for 21-25 year olds, and 32% for 18-20 year olds (32%). The two-year insertion rate for women aged 10-19 was 17.3/1000 compared to 20.8/1000 for women aged 20-29. The implantation rate was greatest among 18-25 year olds and lowest among women aged 26 and older. The method of payment for implantation was medical assistance in 69% of cases and a philanthropic foundation for women not eligible for medical assistance in 29% of cases. 8% had the implants removed during the study period. The leading reason for removal was psychological distress (25%), followed by headaches (20.8%), desire to conceive (16.7%), bleeding (12.5%), and medical contraindication (12.5%). The interval between implantation and removal ranged from less than 3 months to more than 12 months. 2.3% of the female high school students used implants. Among the 596 students who were sexually active, 4.2% used implants, 1.85% used a diaphragm, 27.5% used condoms, and 15% used oral contraceptives. The implant acceptors attended 65% of scheduled 3-month follow-up visits.

Lithium chloride enhances bone regeneration and implant osseointegration in osteoporotic conditions.

PubMed

Jin, Yifan; Xu, Lihua; Hu, Xiaohui; Liao, Shixian; Pathak, Janak L; Liu, Jinsong

2016-10-06

Osteoporotic patients have a high risk of dental and orthopedic implant failure. Lithium chloride (LiCl) has been reported to enhance bone formation. However, the role of LiCl in the success rate of dental and orthopedic implants in osteoporotic conditions is still unknown. We investigated whether LiCl enhances implant osseointegration, implant fixation, and bone formation in osteoporotic conditions. Sprague-Dawley female rats (n = 18) were ovariectomized (OVX) to induce osteoporosis, and another nine rats underwent sham surgery. Three months after surgery, titanium implants were implanted in the tibia of the OVX and sham group rats. After implantation, the OVX rats were gavaged with 150 mg/kg/2 days of LiCl (OVX + LiCl group) or saline (OVX group), and sham group rats were gavaged with saline for 3 months. Implant osseointegration and bone formation were analyzed using histology, biomechanical testing, and micro computed tomography (micro-CT). More bone loss was observed in the OVX group compared to the control, and LiCl treatment enhanced bone formation and implant fixation in osteoporotic rats. In the OVX group, bone-implant contact (BIC) was decreased by 81.2 % compared to the sham group. Interestingly, the OVX + LiCl group showed 4.4-fold higher BIC compared to the OVX group. Micro-CT data of tibia from the OVX + LiCl group showed higher bone volume, trabecular thickness, trabecular number, and osseointegration compared to the OVX group. Maximum push-out force and implant-bone interface shear strength were 2.9-fold stronger in the OVX + LiCl group compared to the OVX group. In conclusion, LiCl enhanced implant osseointegration, implant fixation, and bone formation in osteoporotic conditions, suggesting LiCl as a promising therapeutic agent to prevent implant failure and bone loss in osteoporotic conditions.

Improved Bone Micro Architecture Healing Time after Implant Surgery in an Ovariectomized Rat.

PubMed

Takahashi, Takahiro; Watanabe, Takehiro; Nakada, Hiroshi; Sato, Hiroki; Tanimoto, Yasuhiro; Sakae, Toshiro; Kimoto, Suguru; Mijares, Dindo; Zhang, Yu; Kawai, Yasuhiko

2016-01-01

The present animal study investigated whether oral intake of synthetic bone mineral (SBM) improves peri-implant bone formation and bone micro architecture (BMA). SBM was used as an intervention experimental diet and AIN-93M was used as a control. The SBM was prepared by mixing dicalcium phosphate dihydrate (CaHPO 4 ·2H 2 O) and magnesium and zinc chlorides (MgCl 2 and ZnCl 2 , respectively), and hydrolyzed in double-distilled water containing dissolved potassium carbonate and sodium fluoride. All rats were randomly allocated into one of two groups: a control group was fed without SBM (n = 18) or an experimental group was fed with SBM (n = 18), at seven weeks old. At 9 weeks old, all rats underwent implant surgery on their femurs under general anesthesia. The implant was inserted into the insertion socket prepared at rats' femur to a depth of 2.5 mm by using a drill at 500 rpm. Nine rats in each group were randomly selected and euthanized at 2 weeks after implantation. The remaining nine rats in each group continued their diets, and were euthanized in the same manner at 4 weeks after implantation. The femur, including the implant, was removed from the body and implant was pulled out by an Instron universal testing machine. After the implant removal, BMA was evaluated by bone surface ratio (BS/BV), bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN), trabecular star volume (Vtr), and micro-CT images. BS/BV, BV/TV, TbTh and Vtr were significantly greater in the rats were fed with SBM than those were fed without SBM at 2 and 4 weeks after implantation (P < 0.05). The present results revealed that SBM improves the peri-implant formation and BMA, prominent with trabecular bone structure. The effect of SBM to improve secondary stability of the implant, and shortening the treatment period should be investigated in the future study.

Treatment of diabetic rats with encapsulated islets.

PubMed

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-12-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose>350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30-40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats.

Interval Female Sterilization.

PubMed

Stuart, Gretchen S; Ramesh, Shanthi S

2018-01-01

Female sterilization is relied on by nearly one in three women aged 35-44 years in the United States. Sterilization procedures are among the most common procedures that obstetrician-gynecologists perform. The most frequent sterilization procedures include postpartum tubal ligation, laparoscopic tubal disruption or salpingectomy, and hysteroscopic tubal occlusion. The informed consent process for sterilization is crucial and requires shared decision-making between the patient and the health care provider. Counseling should include the specific risks and benefits of the specific surgical approaches. Additionally, women should be counseled on the alternatives to sterilization, including intrauterine contraceptives and subdermal contraceptive implants. Complications, including unplanned pregnancy after successful female sterilization, are rare. The objectives of this Clinical Expert Series are to describe the epidemiology of female sterilization, access to postpartum sterilization, advances in interval sterilization techniques, and clinical considerations in caring for women requesting sterilization.

Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters.

PubMed

Barfield, A; Melo, J; Coutinho, E; Alvarez-Sanchez, F; Faundes, A; Brache, V; Leon, P; Frick, J; Bartsch, G; Weiske, W H; Brenner, P; Mishell, D; Bernstein, G; Ortiz, A

1979-08-01

A potential male contraceptive approach was evaluated in clinical trials involving monthly injections of depot medroxyprogesterone acetate and either subdermal implants of testosterone propionate or monthly injections of testosterone enanthate. Pregnancies occurred in partners of 9 men with recent sperm counts of 10 million/ml or below. In 5 of the 9 instances, the sperm counts were less than 1 million/ml. It appears that male contraceptive methods involving spermatogenic suppression may require attainment and maintenance of azoospermia. The pregnancy rate cannot be calculated, because the extent of other contraceptive use is uncertain. There were no spontaneous abortions. 6 pregnancies were carried to term, and all progeny were normal, based on physical examination at birth or 3 months after birth.

Enhanced osseointegration of titanium implants in a rat model of osteoporosis using multilayer bone mesenchymal stem cell sheets

PubMed Central

Duan, Yan; Ma, Wei; Li, Dehua; Wang, Tongfei; Liu, Baolin

2017-01-01

The present study aimed to investigate whether bone marrow-derived mesenchymal stem cell (BMSC) sheets combined with titanium implants enhanced implant osseointegration in an ovariectomized (OVX) rat model of osteoporosis. Sprague-Dawley rats were randomly assigned into a test group and control group. Allogenic BMSCs were collected from the rats, cultured and stored via cryopreservation. At 6 months post-ovariectomy, establishment of the OVX model was confirmed by micro-computed tomography (CT) measurements. BMSC sheets were subsequently layered and wrapped over titanium implants for implantation. Unmodified implants served as the control. At 8 weeks post-implantation, samples were observed by micro-CT reconstruction and histomorphometric evaluation. Micro-CT reconstruction identified a marked improvement in the surrounding bone volume following treatment, with data analyses indicating a significant increase in bone volume in the BMSC-implant group compared with the control implant group (P<0.05). In addition, histological staining identified new bone formation and an increased rate of bone-implant contact surrounding the BMSC-implant constructs. These results indicate that the use of BMSC sheets as a novel tissue engineering approach improves the osseointegration of titanium implants in an osteoporosis model. This method may expand the operative indications in patients with osteoporosis and improve the success rate of clinical dental implant treatments. PMID:29250137

Evaluation of vascular effects after photodynamic and photothermal therapies using benzoporphyrin derivative monoacid ring A on a rodent dorsal skinfold model

NASA Astrophysics Data System (ADS)

Smith, Tia K.; Choi, Bernard; Ramirez-San-Juan, Julio C.; Nelson, John S.; Kelly, Kristen M.

2005-04-01

Background and Objectives: Pulsed dye laser (PDL) irradiation is the standard clinical treatment for vascular lesions. However, PDL treatment of port wine stain birthmarks (PWS) is variable and unpredictable. Photodynamic therapy (PDT) using benzoporphyrin derivative monoacid ring A (BPD) and yellow light may induce substantial vascular effects and potentially offer a more effective treatment. In this study, we utilize a rodent dorsal skinfold model to evaluate the vascular effects of BPD-PDT at 576 nm as compared to PDL. Study Design/Materials and Methods: A dorsal skinfold window was created on the backs of female Sprague-Dawley rats, allowing epidermal and subdermal irradiation and subdermal imaging. One mg/kg BPD was administered intravenously via a jugular venous catheter. Study groups were: control (no BPD, no light), PDL (585 nm, τp 1.5 ms, 10 J/cm2), and PDT (BPD + continuous wave irradiation (CW) at 576nm, τp 16 min, 96 J/cm2). Vessels were imaged and assessed for damage using laser speckle imaging (LSI) before, immediately after, and 18 hours post-intervention. Results: Epidermal irradiation was accomplished without blistering, scabbing or ulceration. PDL and PDT resulted in similar reductions in vascular perfusion 18 hours post-intervention (34.6% and 33.4%, respectively). Conclusions: BPD-PDT can achieve safe and selective vascular effects and may offer an alternative therapeutic option for treatment of hypervascular skin lesions including PWS birthmarks.

Biotelemetry implant volume and weight in rats: A pilot study report

NASA Technical Reports Server (NTRS)

Somps, Chris J.

1994-01-01

This paper reports the results of a pilot study in which a 240-gram rat was implanted for 41 days with biotelemetry devices weighing a total of 36 gm (18 cc). The implanted animal showed no differences in weight gain, food and water consumption, and postnecropsy organ weights when compared to both an unoperated control animal and an animal that underwent surgery but did not receive an implant. The implanted animal also had temperature and activity rhythms similar to those reported using much smaller implants. Thus, this pilot study showed that a 240-gm rat could be implanted with biotelemetry devices weighing nearly 15 percent of body weight without significant changes in health or behavior. A larger study involving more animals and similar implant sizes is recommended.

[Differential expression genes of bone tissues surrounding implants in diabetic rats by gene chip].

PubMed

Wang, Xin-xin; Ma, Yue; Li, Qing; Jiang, Bao-qi; Lan, Jing

2012-10-01

To compare mRNA expression profiles of bone tissues surrounding implants between normal rats and rats with diabetes using microarray technology. Six Wistar rats were randomly selected and divided into normal model group and diabetic group. Diabetic model condition was established by injecting Streptozotocin into peritoneal space. Titanium implants were implanted into the epiphyseal end of the rats' tibia. Bone tissues surrounding implant were harvested and sampled after 3 months to perform comprehensive RNA gene expression profiling, including 17983 for genome-wide association study.GO analysis was used to compare different gene expression and real-time PCR was used to confirm the results on core samples. The results indicated that there were 1084 differential gene expression. In the diabetic model, there were 352 enhanced expression genes, 732 suppressed expression genes. GO analysis involved 1154 different functional type. Osteoblast related gene expressions in bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway related gene expression was increased.

Determination of metallic traces in kidneys, livers, lungs and spleens of rats with metallic implants after a long implantation time.

PubMed

Rubio, Juan Carlos; Garcia-Alonso, Maria Cristina; Alonso, Concepcion; Alobera, Miguel Angel; Clemente, Celia; Munuera, Luis; Escudero, Maria Lorenza

2008-01-01

Metallic transfer from implants does not stop at surrounding tissues, and metallic elements may be transferred by proteins to become lodged in organs far from the implant. This work presents an in vivo study of metallic implant corrosion to measure metallic element accumulation in organs located far from the implant, such as kidneys, livers, lungs and spleens. The studied metallic implant materials were CoCr alloy, Ti, and the experimental alloy MA956 coated with alpha-alumina. The implants were inserted in the hind legs of Wistar rats. Analysis for Co, Cr, Ti and Al metallic traces was performed after a long exposure time of 12 months by Inductively Coupled Plasma (ICP) with Mass Spectrometry (MS). According to the results, the highest Cr and Ti concentrations were detected in spleens. Co is mainly found in kidneys, since this element is eliminated via urine. Cr and Ti traces increased significantly in rat organs after the long implantation time. The organs of rats implanted with the alpha-alumina coated experimental MA956 did not present any variation in Al content after 12 months, which means there was no degradation of the alumina layer surface.

Treatment of diabetic rats with encapsulated islets

PubMed Central

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-01-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte™ immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose >350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30–40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte™ devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats. PMID:18373735

A Fully Implanted Drug Delivery System for Peripheral Nerve Blocks in Behaving Animals

PubMed Central

Pohlmeyer, Eric A.; Jordon, Luke R.; Kim, Peter; Miller, Lee E.

2009-01-01

Inhibiting peripheral nerve function can be useful for many studies of the nervous system or motor control. Accomplishing this in a temporary fashion in animal models by using peripheral nerve blocks permits studies of the immediate effects of the loss, and/or any resulting short-term changes and adaptations in behavior or motor control, while avoiding the complications commonly associated with permanent lesions, such as sores or self-mutilation. We have developed a method of quickly and repeatedly inducing temporary, controlled motor deficits in rhesus macaque monkeys via a chronically implanted drug delivery system. This assembly consists of a nerve cuff and a subdermal injection dome, and has proved effective for delivering local anesthetics directly to peripheral nerves for many months. Using this assembly for median and ulnar nerve blocks routinely resulted in over 80% losses in hand and wrist strength for rhesus monkeys. The assembly was also effective for inducing ambulatory motor deficits in rabbits through blocks of the sciatic nerve. Interestingly, while standard anesthetics were sufficient for the rabbit nerve blocks, the inclusion of epinephrine was essential for achieving significant motor blockade in the monkeys. PMID:19524613

The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine.

PubMed

Neary, M; Lamorde, M; Olagunju, A; Darin, K M; Merry, C; Byakika-Kibwika, P; Back, D J; Siccardi, M; Owen, A; Scarsi, K K

2017-09-01

Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based antiretroviral therapy (ART), in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log 10 C max and log 10 AUC. CYP2B6 15582C>T was associated with lower log 10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log 10 C max and lower log 10 C min . Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Possible sources of neuroprotection following subretinal silicon chip implantation in RCS rats

NASA Astrophysics Data System (ADS)

Pardue, Machelle T.; Phillips, Michael J.; Yin, Hang; Fernandes, Alcides; Cheng, Yian; Chow, Alan Y.; Ball, Sherry L.

2005-03-01

Current retinal prosthetics are designed to stimulate existing neural circuits in diseased retinas to create a visual signal. However, implantation of retinal prosthetics may create a neurotrophic environment that also leads to improvements in visual function. Possible sources of increased neuroprotective effects on the retina may arise from electrical activity generated by the prosthetic, mechanical injury due to surgical implantation, and/or presence of a chronic foreign body. This study evaluates these three neuroprotective sources by implanting Royal College of Surgeons (RCS) rats, a model of retinitis pigmentosa, with a subretinal implant at an early stage of photoreceptor degeneration. Treatment groups included rats implanted with active and inactive devices, as well as sham-operated. These groups were compared to unoperated controls. Evaluation of retinal function throughout an 18 week post-implantation period demonstrated transient functional improvements in eyes implanted with an inactive device at 6, 12 and 14 weeks post-implantation. However, the number of photoreceptors located directly over or around the implant or sham incision was significantly increased in eyes implanted with an active or inactive device or sham-operated. These results indicate that in the RCS rat localized neuroprotection of photoreceptors from mechanical injury or a chronic foreign body may provide similar results to subretinal electrical stimulation at the current output evaluated here.

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

PubMed Central

Kalinich, John F.; Emond, Christy A.; Dalton, Thomas K.; Mog, Steven R.; Coleman, Gary D.; Kordell, Jessica E.; Miller, Alexandra C.; McClain, David E.

2005-01-01

Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys. PMID:15929896

Xenotransplantation of uterine leiomyoma in Wistar rats: a pilot study.

PubMed

Sousa, Willane Bandeira de; Garcia, João Batista Santos; Nogueira Neto, João; Furtado, Pablo Gustavo Ribeiro; Anjos, Jonhnathan Adriano Araújo dos

2015-07-01

To evaluate whether xenografts derived from hysterectomized patients would implant successfully and lead to uterine leiomyoma in Wistar rats. This experimental study examined six female Wistar rats implanted with uterine leiomyoma obtained from patients who underwent hysterectomies at the gynecological surgery service of the HUUFMA. The rats were divided into two groups. Group I consisted of three rats in which the uterine leiomyoma had been implanted in the parietal peritoneum, and group II consisted of three rats in which the uterine leiomyoma was implanted in the subcutaneous tissue. The immunosuppressant mycophenolate mofetil (MMF) was administered orally by gavage (at a dose of 40 mg/kg of body weight) to prevent transplant rejection starting 15 days before the transplant and continuing throughout the entire experiment. After four weeks, necrosis and neovascularization were evaluated histologically in both groups and were classified as either absent or present. Lymphocytic inflammatory infiltration was also examined and classified as mild, moderate or intense (by hematoxylin and eosin staining), and fibrosis was classified as grade I-III (by Masson's trichrome staining). Necrosis was absent from all three rats in group I and was observed in only one rat from group II. Neovascularization was present in two rats from group I and in only one rat from group II. The lymphocytic inflammatory infiltrate was mild in two rats and moderate in one rat from group I, and it was moderate in two rats and intense in one rat from group II. Two rats from group 1 exhibited grade III fibrosis, and one rat presented grade I fibrosis. In group II, two rats presented grade I fibrosis and one rat had grade II fibrosis. When necrosis and neovascularization were evaluated as variables, group I demonstrated greater evidence of successful implantation when compared to group II, indicating that the peritoneal implantation technique produces better results than the subcutaneous approach (p=0.039). This study demonstrates that the xenotransplantation of uterine leiomyoma into the parietal peritoneum is more effective than the xenotransplantation of uterine leiomyoma into the subcutaneous tissue, and it describes a promising new model for the study of leiomyoma in vivo. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Different Approach for Usage of the Implant Materials: The Composite Graft Prefabrication.

PubMed

Deniz, Lutfi Murat; Ataman, Murat Görkem; Borman, Huseyin; Erinanç, Hilal

2016-10-01

With all implanted materials, a certain sequence of biological events occurs following the implantation. This process is destructive to the implant and peri-implant tissues. The aforementioned sequence of biological events may be responsible for the complications. In this study, the natural biologic process following implantation was completed in an area other than the final implantation area. The aim was to keep the peri-implant tissues in the final implantation area away from the process. In the control group, the porous polyethylene discs were implanted to subcutaneous area on the frontal bone of the rats. A month after the implantation, macroscopic and microscopic examinations were performed. In the study group, the discs were implanted primarily above the rectus abdominis muscle of the rats. It was named as "the composite graft prefabrication." Twenty-one days after the first implantation, the discs were removed from the rectus muscle and implanted to subcutaneous area on the frontal bone of the rats. A month after the final implantation, macroscopic and microscopic examinations were performed. In macroscopic examination, all possible complications were evaluated. In microscopic examination, apoptosis, fibrosis, inflammation, and fibrovascular in-growing were evaluated. In the control group, implant exposure was observed in 3 of the rats. In the study group, no complications were observed. Although there was no statistical difference between 2 groups in the microscopic findings, at first glance, the inflammation seemed to be the factor responsible for the complication in the control group. According to the macroscopic results, the composite graft prefabrication seemed to be effective in preventing complications.

SEMA3A suspended in matrigel improves titanium implant fixation in ovariectomized rats.

PubMed

Li, Yunfeng; He, Dongming; Liu, Biao; Hu, Jing

2017-10-01

The aim of this study was to evaluate the effect of SEMA3A released from matrigel on implant fixation in ovariectomized (OVX) rats. Sixty female rats were subjected to bilateral ovariectomy. Twelve weeks later, rats were randomly divided into three groups according to implants they accepted: (1) Control, implants with distilled water; (2) Matrigel, implants with matrigel coating; (3) Matrigel + SEMA3A, implants with coating of SEMA3A suspended in matrigel. Implants were inserted in metaphysis of proximal tibiae in all animas bilaterally. In vitro release of SEMA3A was tested using enzyme linked immunosorbent assay. In vitro release of SEMA3A was detectable during the first 10 days, and a burst release of was observed during the first 3 days. No significant difference was observed between Control and Matrigel group. The protective effects of SEMA3A in matrigel on peri-implant bone, implant osseointegration and fixation was confirmed. Compared to matrigel alone, SEMA3A suspended in matrigel increased percent bone volume by 88.7% and 83.3% (p < 0.01), bone-to-implant contact ratio by 148.9% (p < 0.01), and 24.8% (p < 0.05), the maximal push-out force by 149.3% and 209.2% (p < 0.01) at 4 and 8 weeks after implant insertion, respectively. Surface modification with SEMA3A suspended in matrigel improved implant osseointegration and fixation in the proximal tibiae of OVX rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2060-2065, 2017. © 2016 Wiley Periodicals, Inc.

Neuroprotective effect of subretinal implants in the RCS rat.

PubMed

Pardue, Machelle T; Phillips, Michael J; Yin, Hang; Sippy, Brian D; Webb-Wood, Sarah; Chow, Alan Y; Ball, Sherry L

2005-02-01

Retinal prosthetics have been designed to interface with the neural retina by electrically stimulating the remaining retinal circuits after photoreceptor degeneration. However, the electrical stimulation provided by the subretinal implant may also stimulate neurotrophic factors that provide neuroprotection to the retina. This study was undertaken to determine whether electrical stimulation from a subretinal photodiode-based implant has a neuroprotective effect on photoreceptors in the RCS rat, a model of photoreceptor degeneration. Eyes of RCS rats were implanted with an active or inactive device or underwent sham surgery before photoreceptor degeneration. Outer retinal function was assessed with electroretinogram (ERG) recordings weekly until 8 weeks after surgery, at which time retinal tissue was collected and processed for morphologic assessment, including photoreceptor cell counts and retinal layer thickness. At 4 to 6 weeks after surgery, the ERG responses in the active-implant eyes were 30% to 70% greater in b-wave amplitude than the responses from eyes implanted with inactive devices, those undergoing sham surgery, or the nonsurgical control eyes. At 8 weeks after surgery the ERG responses from active-implant eyes were not significantly different from the control groups. However, the number of photoreceptors in eyes implanted with the active or inactive device was significantly greater in the regions over and around the implant versus sham-surgical and nonsurgical control eyes. These results suggest that subretinal electrical stimulation provides temporary preservation of retinal function in the RCS rat. In addition, implantation of an active or inactive device into the subretinal space causes morphologic preservation of photoreceptors in the RCS rat until 8 weeks after surgery. Further studies are needed to determine whether the correlation of neuropreservation with subretinal implantation is due to electrical stimulation and/or a mechanical presence of the implant in the subretinal space.

A comparative evaluation of the tissue responses associated with polymeric implants in the rat and mouse.

PubMed

Kidd, Kameha R; Dal Ponte, Donny B; Kellar, Robert S; Williams, Stuart K

2002-03-15

End product application is an important consideration when evaluating a material in an in vivo setting (Didisheim, Cardiovasc Pathol 1993;2:1S-2S). Small animal models allow high through-put evaluation of biocompatability. Previous preclinical evaluations have often used a rat subcutaneous model for the characterization of material-tissue interaction. Recent advances in genetic manipulation have provided mouse models with selective expression of a wide range of critical proteins. The rat model does not have many of the resources (i.e., knockouts, SCID, nude) that are present in mouse strains. The availability of these mice provides a resource to delineate the mechanisms regulating the healing associated with implants. However, before the mouse models can be used, they must be validated with respect to their ability to accurately assess tissue responses to materials. In this study the tissue responses after the implantation of expanded polytetrafluoroethylene (ePTFE) were compared between rat and mouse. Discs of ePTFE (30-microm internodal distance) were implanted in subcutaneous and epididymal fat tissue of rats (Sprague-Dawley) and mice (129-SVJ). After 5 weeks the samples were removed and evaluated for vascular density, inflammation, and fibrous encapsulation. No difference in the vessel density was observed within the peri-implant subcutaneous and adipose tissue or within the porous material. However, a significant difference was found in the number of activated macrophages and giant cells between these two species. Implants in the rat exhibited greater numbers of activated inflammatory cells in the peri-implant tissue. The data indicate that the mouse and rat provide a comparable model for evaluating angiogenesis and neovascularization associated with synthetic porous implants. Copyright 2001 John Wiley & Sons, Inc. J Biomed Mater Res 59: 682-689, 2002

Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis.

PubMed

Alamusi; Matsuo, Toshihiko; Hosoya, Osamu; Tsutsui, Kimiko M; Uchida, Tetsuya

2013-09-01

We have developed a photoelectric dye-coupled polyethylene film as a prototype of retinal prosthesis, which we named Okayama University-type retinal prosthesis. The purposes of this study are to conduct behavior tests to assess vision in Royal College of Surgeons (RCS) rats that underwent subretinal implantation of the dye-coupled film and to reveal retinal response to the dye-coupled film by immunohistochemistry. Polyethylene films were made of polyethylene powder at refined purity, and photoelectric dyes were coupled to the film surface at higher density compared with the prototype. Either dye-coupled film or dye-uncoupled plain film used as a control was implanted subretinally from a scleral incision in both eyes of an RCS rat at 6 weeks of the age. Behavior tests 2, 4, 6, and 8 weeks after implantation were conducted by observing head turning or body turning in the direction consistent with clockwise or counterclockwise rotation of a black-and-white-striped drum around a transparent cage housed with the rat. After the behavior tests at 8 weeks, rats' eyes were enucleated to confirm subretinal implantation of the films and processed for immunohistochemistry. In the behavior tests, the number of head turnings consistent with the direction of the drum rotation was significantly larger in RCS rats with dye-coupled- compared with plain-film implantation [P < 0.05, repeated-measure analysis of variance (ANOVA), n = 7]. The number of apoptotic neurons was significantly smaller in eyes with dye-coupled- compared with plain-film implantation (P < 0.05, Mann-Whitney U test, n = 6). In conclusion, subretinal implantation of photoelectric dye-coupled films restored vision in RCS rats and prevented the remaining retinal neurons from apoptosis.

Avoiding and treating dermal filler complications.

PubMed

Lemperle, Gottfried; Rullan, Peter P; Gauthier-Hazan, Nelly

2006-09-01

All fillers are associated with the risk of both early and late complications. Early side effects such as swelling, redness, and bruising occur after intradermal or subdermal injections. The patient has to be aware of and accept these risks. Adverse events that last longer than 2 weeks can be attributable to technical shortcomings (e.g., too superficial an implantation of a long-lasting filler substance). Such adverse events can be treated with intradermal 5-fluorouracil, steroid injections, vascular lasers, or intense pulsed light, and later with dermabrasion or shaving. Late adverse events also include immunologic phenomena such as late-onset allergy and nonallergic foreign body granuloma. Both react well to intralesional steroid injections, which often have to be repeated to establish the right dose. Surgical excisions shall remain the last option and are indicated for hard lumps in the lips and visible hard nodules or hard granuloma in the subcutaneous fat.

Noninvasive selective cryolipolysis and reperfusion recovery for localized natural fat reduction and contouring.

PubMed

Sasaki, Gordon H; Abelev, Natalie; Tevez-Ortiz, Ana

2014-03-01

Cryolipolysis is a contemporary method of reducing fat by controlled extraction of heat from adipocytes. The authors recorded temperature profiles during a single cryolipolysis treatment/recovery cycle (with and without massage) and report on the clinical safety and efficacy of this procedure. In the pilot study group (PSG), the abdomens of 6 patients were treated with cryolipolysis and subdermal temperatures were recorded. In the clinical treatment group (CTG), 112 patients were treated without temperature recordings and results were evaluated through matched comparison of standardized photographs, caliper measurements, ultrasound imaging, and global assessments. Thirty minutes into the cooling phase, subdermal temperatures of patients in the PSG declined precipitously from pretreatment levels and remained low until the end of treatment. During recovery, subdermal temperatures of the only subject who received massage returned faster and to higher levels than the temperatures of subjects who did not receive massage. Patients in the CTG who were available for follow-up measurements at 6 months (n = 85) demonstrated an average fat reduction of 21.5% by caliper measurements; 6 random patients from this group also showed an average of 19.6% fat reduction by ultrasound imaging at 6 months. Global assessments were highest for the abdomen, hip, and brassiere rolls. Minimal side effects were observed, and patients experienced no significant downtime. Noninvasive cryolipolysis results in a predictable and noticeable fat reduction within 6 months and does not cause skin damage. Profiling of subdermal temperatures may provide additional insights for improving clinical effectiveness and safety. 3.

Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel.

PubMed

Funk, Sidney; Miller, Michael M; Mishell, Daniel R; Archer, David F; Poindexter, Alfred; Schmidt, Juergen; Zampaglione, Edio

2005-05-01

The safety and efficacy of a single-rod implantable contraceptive containing etonogestrel (Implanontrade mark) were investigated in a multicenter clinical trial. Sexually active American women (N=330) with apparently normal menstrual cycles used the implant for up to 2 years. All subjects recorded bleeding and/or spotting daily in a diary. Safety was assessed through adverse experiences (AEs), laboratory tests and physical and gynecologic examinations. Total exposure was 474 woman-years (6186 cycles), and 68% of subjects had at least 1 year of exposure. No pregnancies occurred. The most common bleeding pattern observed throughout the study was infrequent bleeding, defined as less than three episodes of bleeding in a reference period (excluding amenorrhea). The least common pattern was frequent bleeding, defined as more than five episodes of bleeding in a reference period. Infrequent, prolonged and frequent bleeding patterns were most common early in the study and declined thereafter. During the 3-month Reference Periods 2-8 (Months 4-24), the incidence of amenorrhea ranged from 14% to 20%. Forty-three subjects (13%) withdrew from the study because of bleeding pattern changes and 76 subjects (23%) discontinued because of other AEs. Other common AEs leading to discontinuation, besides bleeding irregularities, were emotional lability (6.1%), weight increase (3.3%), depression (2.4%) and acne (1.5%). Use of Implanon (etonogestrel subdermal implant, referred to herein as ENG implant) for up to 2 years had no clinically significant effects on laboratory parameters, physical and pelvic examinations, vital signs or body mass index. The average length of time required for ENG implant insertion and that for removal were 0.5 and 3.5 min, respectively, and all the procedures were uncomplicated. The return to normal menstrual cycles and fertility was rapid after removal. Implanon is a safe, highly effective and rapidly reversible new method of contraception.

A microcontroller-based implantable nerve stimulator used for rats.

PubMed

Sha, Hong; Zheng, Zheng; Wang, Yan; Ren, Chaoshi

2005-01-01

A microcontroller-based stimulator that can be flexible programmed after it has been implanted into a rat was studied. Programmability enables implanted stimulators to generate customized, complex protocols for experiments. After implantation, a coded light pulse train that contains information of specific identification will unlock a certain stimulator. If a command that changing the parameters is received, the microcontroller will update its flash memory after it affirms the commands. The whole size of it is only 1.6 cubic centimeters, and it can work for a month. The devices have been successfully used in animal behavior experiments, especially on rats.

Fertility of male rats treated with 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic implants.

PubMed

Kimball, F A; Frielink, R D; Porteus, S E

1978-01-01

Male Spraque-Dawley rats receiving implants of silicone rubber discs containing 1% or 2% 15(S)-15-methyl prostaglandin F2 alpha methyl ester (15-Me-PGF 2 alpha) or no prostaglandin were tested in successive breeding trials for potency and fertility. One week after implantation, discs containing 1% 15-Me-PGF2 alpha reduced potency and fertility, which returned 2 weeks after implantation. Animals receiving implants of the 2% discs were apparently impotent the 1st week following implantation; potency returned before full fertility returned 11 weeks after implantation.

Assessing the validity and reliability of self-report data on contraception use in the MObile Technology for Improved Family Planning (MOTIF) randomised controlled trial.

PubMed

Smith, Chris; Edwards, Phil; Free, Caroline

2018-03-15

A variety of different approaches to measuring contraceptive use have been used or proposed, either to assess current use or adherence over time, using subjective or objective measures. This paper reports an overview of approaches to measuring adherence to the oral contraceptive, intra-uterine device, sub-dermal implant, and injectable and describes how we assessed contraception use in the MObile Technology for Improved Family Planning (MOTIF) trial in Cambodia. We summarise and discuss advantages and disadvantages of different subjective and objective approaches to measuring adherence to the oral contraceptive, intra-uterine device, sub-dermal implant, and injectable such as self-reports, clinic records, electronic monitoring devices, clinical examination and biomarkers. For the MOTIF trial, we did not consider it feasible to measure objective contraception use as many participants lived a long distance from the clinic and we were concerned whether it was appropriate to ask women to return to clinic for a physical examination simply to verify self-report information already provided. We aimed to assess the validity of the four-month data with 50 participants, calculating the sensitivity and specificity of self-reported data compared with objective measurement. For the 46 valid measurements obtained, the sensitivity and specificity was 100% for self-reported contraception use compared to objective measurement but this study had some limitations. To assess reliability of self-report data we compared calendar data collected on effective contraception use at months 1-4 post-abortion, collected separately at four and 12 months. Agreement ranged from 80 to 84% with a kappa statistic ranging from 0·59 to 0·67 indicating fair to good agreement. There is no perfect method of assessing contraception use and researchers designing future studies should give consideration of what to measure, for example current use or detailed patterns of use over time, and remain mindful of what will be feasible and acceptable to the study population. Although self-reported data on contraception use are considered less reliable, and prone to social desirability bias, it is often the standard approach for contraception research and provides data comparable to previous studies. ClinicalTrials.gov Identifier: NCT01823861 . Registered: March 30, 2013.

In vivo evaluation of teicoplanin- and calcium sulfate-loaded PMMA bone cement in preventing implant-related osteomyelitis in rats.

PubMed

Tuzuner, T; Sencan, I; Ozdemir, D; Alper, M; Duman, S; Yavuz, T; Yildirim, M

2006-12-01

The objective of this study was to evaluate the efficacy of teicoplanin- and calcium sulphate-loaded polymethylmethacrylate (PMMA) bone cements in preventing experimental implant-related osteomyelitis in rats. Four groups of antibiotic-loaded rods were prepared and were implanted into the lateral condylus of the rat femur after inoculation of Staphylococcus aureus. The effectiveness of these were assessed microbiologically, radiographically, and histopathologically. Radiographic evaluation revealed a significant reduction of periostal reaction and osteolysis in rats that received calcium sulphate- and teicoplanin-loaded rods. Histopathological evaluation confirmed these results. Acute infection and bone necrosis were found to be significantly lower in rats that had received calcium sulphate- and teicoplanin-loaded rods. The addition of calcium sulfate to teicoplanin-loaded PMMA bone cement appeared satisfactory as an antibiotic-carrying system for prophylaxis of experimental implant-related osteomyelitis, but further investigations are needed to reach definitive statements for clinical applications.

Influences of serum from ozone-exposed pregnant rats in an in vitro model of implantation

EPA Science Inventory

In our previous studies, ozone (O3) exposure during implantation [gestational day (GD) 5 and 6)] in rats resulted in intrauterine growth restriction (IUGR), suggesting impairment of implantation with exposure. The aim of this study was to (1) determine if serum collected from pre...

Contraceptive effect and potential side-effects of deslorelin acetate implants in rats (Rattus norvegicus): Preliminary observations

PubMed Central

Grosset, Claire; Peters, Stijn; Peron, Franck; Figuéra, Joëlle; Navarro, Christelle

2012-01-01

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study. PMID:23277700

Early bone growth on the surface of titanium implants in rat femur is enhanced by an amorphous diamond coating.

PubMed

Jaatinen, Jarkko J P; Korhonen, Rami K; Pelttari, Alpo; Helminen, Heikki J; Korhonen, Hannu; Lappalainen, Reijo; Kröger, Heikki

2011-08-01

Amorphous diamond (AD) is a durable and compatible biomaterial for joint prostheses. Knowledge regarding bone growth on AD-coated implants and their early-stage osseointegration is poor. We investigated bone growth on AD-coated cementless intramedullary implants implanted in rats. Titanium was chosen as a reference due to its well-known performance. We placed AD-coated and non-coated titanium implants (R(a) ≈ 0.2 μm) into the femoral bone marrow of 25 rats. The animals were divided in 2 groups according to implant coating and they were killed after 4 or 12 weeks. The osseointegration of the implants was examined from hard tissue specimens by measuring the new bone formation on their surface. 4 weeks after the operation, the thickness of new bone in the AD-coated group was greater than that in the non-coated group (15.3 (SD 7.1) μm vs. 7.6 (SD 6.0) μm). 12 weeks after the operation, the thickness of new bone was similar in the non-coated group and in the AD-coated group. We conclude that AD coating of femoral implants can enhance bone ongrowth in rats in the acute, early stage after the operation and might be an improvement over earlier coatings.

Histologic evaluation of laser lipolysis comparing continuous wave vs pulsed lasers in an in vivo pig model.

PubMed

Levi, Jessica R; Veerappan, Anna; Chen, Bo; Mirkov, Mirko; Sierra, Ray; Spiegel, Jeffrey H

2011-01-01

To evaluate acute and delayed laser effects of subdermal lipolysis and collagen deposition using an in vivo pig model and to compare histologic findings in fatty tissue after continuous wave diode (CW) vs pulsed laser treatment. Three CW lasers (980, 1370, and 1470 nm) and 3 pulsed lasers (1064, 1320, and 1440 nm) were used to treat 4 Göttingen minipigs. Following administration of Klein tumescent solution, a laser cannula was inserted at the top of a 10 × 2.5-cm rectangle and was passed subdermally to create separate laser "tunnels." Temperatures at the surface and at intervals of 4-mm to 20-mm depths were recorded immediately after exposure and were correlated with skin injury. Full-thickness cutaneous biopsy specimens were obtained at 1 day, 1 week, and 1 month after exposure and were stained with hematoxylin-eosin and trichrome stain. Qualitative and semiquantitative histopathologic evaluations were performed with attention to vascular damage, lipolysis, and collagen deposition. Skin surface damage occurred at temperatures exceeding 46°C. Histologic examination at 1 day after exposure showed hemorrhage, fibrous collagen fiber coagulation, and adipocyte damage. Adipocytes surrounded by histiocytes, a marker of lipolysis, were present at 1 week and 1 month after exposure. Collagen deposition in subdermal fatty tissue and in reticular dermis of some specimens was noted at 1 week and had increased at 1 month. Tissue treated with CW laser at 1470 nm demonstrated greater hemorrhage and more histiocytes at damage sites than tissue treated with pulsed laser at 1440 nm. There was a trend toward more collagen deposition with pulsed lasers than with CW lasers, but this was not statistically significant. Histopathologic comparison between results of CW laser at 980 nm vs pulsed laser at 1064 nm showed the same trend. Hemorrhage differences may result from pulse duration variations. A theoretical calculation estimating temperature rise in vessels supported this hypothesis. Pulsed lasers with higher peak powers provided better hemostatic effects than CW lasers. The degree of lipolysis depended on wavelength, laser power, and energy density. Subdermal laser irradiation can stimulate collagen deposition in subdermal tissue and reticular dermis.

Concomitant contraceptive implant and efavirenz use in women living with HIV: perspectives on current evidence and policy implications for family planning and HIV treatment guidelines

PubMed Central

Patel, Rena C.; Morroni, Chelsea; Scarsi, Kimberly K.; Sripipatana, Tabitha; Kiarie, James; Cohen, Craig R.

2017-01-01

Abstract Introduction: Preventing unintended pregnancies is important among all women, including those living with HIV. Increasing numbers of women, including HIV-positive women, choose progestin-containing subdermal implants, which are one of the most effective forms of contraception. However, drug–drug interactions between contraceptive hormones and efavirenz-based antiretroviral therapy (ART) may reduce implant effectiveness. We present four inter-related perspectives on this issue. Discussion: First, as a case study, we discuss how limited data prompted country-level guidance against the use of implants among women concomitantly using efavirenz in South Africa and its subsequent negative effects on the use of implants in general. Second, we discuss the existing clinical data on this topic, including the observational study from Kenya showing women using implants plus efavirenz-based ART had three-fold higher rates of pregnancy than women using implants plus nevirapine-based ART. However, the higher rates of pregnancy in the implant plus efavirenz group were still lower than the pregnancy rates among women using common alternative contraceptive methods, such as injectables. Third, we discuss the four pharmacokinetic studies that show 50–70% reductions in plasma progestin concentrations in women concurrently using efavirenz-based ART as compared to women not on any ART. These pharmacokinetic studies provide the biologic basis for the clinical findings. Fourth, we discuss how data on this topic have marked implications for both family planning and HIV programmes and policies globally. Conclusion: This controversy underlines the importance of integrating family planning services into routine HIV care, counselling women appropriately on increased risk of pregnancy with concomitant implant and efavirenz use, and expanding contraceptive method mix for all women. As global access to ART expands, greater research is needed to explore implant effectiveness when used concomitantly with newer ART regimens. Data on how HIV-positive women and their partners choose contraceptives, as well as information from providers on how they present and counsel patients on contraceptive options are needed to help guide policy and service delivery. Lastly, greater collaboration between HIV and reproductive health experts at all levels are needed to develop successful strategies to ensure the best HIV and reproductive health outcomes for women living with HIV. PMID:28530033

Concomitant contraceptive implant and efavirenz use in women living with HIV: perspectives on current evidence and policy implications for family planning and HIV treatment guidelines.

PubMed

Patel, Rena C; Morroni, Chelsea; Scarsi, Kimberly K; Sripipatana, Tabitha; Kiarie, James; Cohen, Craig R

2017-05-11

Preventing unintended pregnancies is important among all women, including those living with HIV. Increasing numbers of women, including HIV-positive women, choose progestin-containing subdermal implants, which are one of the most effective forms of contraception. However, drug-drug interactions between contraceptive hormones and efavirenz-based antiretroviral therapy (ART) may reduce implant effectiveness. We present four inter-related perspectives on this issue. First, as a case study, we discuss how limited data prompted country-level guidance against the use of implants among women concomitantly using efavirenz in South Africa and its subsequent negative effects on the use of implants in general. Second, we discuss the existing clinical data on this topic, including the observational study from Kenya showing women using implants plus efavirenz-based ART had three-fold higher rates of pregnancy than women using implants plus nevirapine-based ART. However, the higher rates of pregnancy in the implant plus efavirenz group were still lower than the pregnancy rates among women using common alternative contraceptive methods, such as injectables. Third, we discuss the four pharmacokinetic studies that show 50-70% reductions in plasma progestin concentrations in women concurrently using efavirenz-based ART as compared to women not on any ART. These pharmacokinetic studies provide the biologic basis for the clinical findings. Fourth, we discuss how data on this topic have marked implications for both family planning and HIV programmes and policies globally. This controversy underlines the importance of integrating family planning services into routine HIV care, counselling women appropriately on increased risk of pregnancy with concomitant implant and efavirenz use, and expanding contraceptive method mix for all women. As global access to ART expands, greater research is needed to explore implant effectiveness when used concomitantly with newer ART regimens. Data on how HIV-positive women and their partners choose contraceptives, as well as information from providers on how they present and counsel patients on contraceptive options are needed to help guide policy and service delivery. Lastly, greater collaboration between HIV and reproductive health experts at all levels are needed to develop successful strategies to ensure the best HIV and reproductive health outcomes for women living with HIV.

Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

PubMed

Nasongkla, Norased; Boongird, Atthaporn; Hongeng, Suradej; Manaspon, Chawan; Larbcharoensub, Noppadol

2012-02-01

We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 μl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 μl were tolerated relatively well compared to those of 25 and 40 μl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

Vision maintenance and retinal apoptosis reduction in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation.

PubMed

Alamusi; Matsuo, Toshihiko; Hosoya, Osamu; Tsutsui, Kimiko M; Uchida, Tetsuya

2015-09-01

Photoelectric dye-coupled polyethylene film, designated Okayama University-type retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. In this study, the vision was assessed by behavior tests in aged hereditary retinal dystrophic RCS rats with OUReP™, retinal apoptosis and electroretinographic responses were measured in dystrophic eyes with OUReP™. The dye-coupled films, or plain films as a control, were implanted in subretinal space of RCS rats. On behavior tests, RCS rats with dye-coupled films, implanted at the old age of 14 weeks, showed the larger number of head-turning, consistent with clockwise and anticlockwise rotation of a surrounding black-and-white-striped drum, compared with rats with plain films, under the dim (50 lux) and bright (150 lux) conditions in the observation period until the age of 22 weeks (n = 5, P < 0.05, repeated-measure ANOVA). The number of apoptotic cells in retinal sections at the site of dye-coupled film implantation was significantly smaller, compared with the other retinal sites, neighboring the film, or opposite to the film, 5 months after film implantation at the age of 6 weeks (P = 0.0021, Friedman test). The dystrophic eyes of RCS rats with dye-coupled films showed positive responses to maximal light stimulus at a significantly higher rate, compared with the eyes with no treatment (P < 0.05, Chi-square test). Electroretinograms in normal eyes of Wistar rats with dye-coupled or plain films showed significantly decreased amplitudes (n = 14, P < 0.05, repeated-measure ANOVA). In conclusions, vision was maintained in RCS rats with dye-coupled films implanted at the old age. The dystrophic eyes with dye-coupled films showed electroretinographic responses. Five-month film implantation caused no additional retinal changes.

Isolation of intact sub-dermal secretory cavities from Eucalyptus

PubMed Central

2010-01-01

Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h), with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain. PMID:20807444

Bone regeneration by recombinant human bone morphogenetic protein-2 around immediate implants: a pilot study in rats.

PubMed

Matin, Khalrul; Senpuku, Hidenobu; Hanada, Nobuhiro; Ozawa, Hidehiro; Ejiri, Sadakazu

2003-01-01

Difficulties relating to bone regeneration that complicate immediate implant placement include buccal and/or lingual fenestrations, primary anchorage of the implants, and the need for protection from functional loading during the osseointegration period. The objective of this pilot study was to evaluate bone regeneration by recombinant human bone morphogenetic protein-2 (rhBMP-2) around immediate implants placed in maxillary sockets in rats. A total of 16 cylindric 0.8 x 1.8-mm commercially pure, solid titanium Implants were placed immediately after gentle extraction of the maxillary first molar teeth of 8 male Wistar rats. The sockets were randomly divided into 3 groups: group 1 (n = 6) received rhBMP-2 with polylactic acid/polyglycolic acid copolymer-coated gelatin sponge carrier; group 2 (n = 5) received only the carrier; and group 3 (n = 5) received no grafting materials following placement The rats were euthanized at 90 days postsurgery for microscopic analysis. In group 1, the implant body remained submerged completely, including the coronal part, which was fully covered by a significant amount (30% of total height) of regenerated cortical bone, even though the implant could easily be pulled out by a tweezer at the time of placement. Close approximation between the implant surface and regenerated bone could also be detected, indicating good bone-to-implant contact. In contrast, only peri-implant bone regeneration occurred in group 2, and an approximate 0.3-mm coronal part of the implant remained exposed. When no grafting materials were used (group 3), almost one third of the total length of the implant was exfoliated out of the socket when no grafting materials were used. Based on previous study and data from 16 sockets of the present study, it could be concluded that rhBMP-2 facilitated the regeneration of bone around immediate implants. In particular, the bone covering the coronal part could have been regenerated shortly after surgery, which helped to maintain the implant body inside the socket during the integration period in rats.

Somatostatin analogs regress endometriotic implants in rats by decreasing implant levels of vascular endothelial growth factor and matrix metaloproteinase 9.

PubMed

Sevket, Osman; Sevket, Asli; Molla, Taner; Buyukpınarbasılı, Nur; Uysal, Omer; Yılmaz, Bulent; Dane, Banu; Kelekcı, Sefa

2013-06-01

To examine the effect of somatostatin analogs on surgically induced endometriosis in rat models. Endometrial tissue was implanted onto the abdominal peritoneum of 26 rats that were randomized into 3 groups. The rats in group 1(n = 9) were subcutaneously administered with 0.02 mg/kg/d of octreotide (a short-acting analog)for 28 days . The rats in group 2 (n = 8) were subcutaneously injected with 20 mg/kg of a single dose of a long-acting analogue lanreotide The rats in group 3 were given no medication and served as controls (n = 9). Mean volume and histologic score of implants in groups 1 (P < .01 and P < .05, respectively) and 2 (P < .01and P < .05, respectively) were significantly lower than that in group 3. There were significant reductions in vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) immunoreactivities in group 1 (0.67 ± 0.50 and 1.22 ± 0.44, respectively; both P < .01) and group 2 (0.71 ± 0.48 and 0.86 ± 0.69, respectively; both P < .01) when compared with the control group (1.78 ± 0.83 and 2.11 ± 0.78, respectively). Somatostatin analogs has regressed significantly the size of the endometriotic implants and caused atrophy of these lesions in rats by decreasing explant levels of VEGF and MMP-9.

Photoacoustic imaging of angiogenesis in subdermal islet transplant sites

NASA Astrophysics Data System (ADS)

Shi, Wei; Pawlick, Rena; Bruni, Antonio; Rafiei, Yasmin; Pepper, Andrew R.; Gala-Lopez, Boris; Choi, Min; Malcolm, Andrew; Zemp, Roger J.; Shapiro, A. M. James

2016-03-01

Exogenous insulin administration is the mainstay treatment therapy for patients with Type-1 diabetes mellitus (T1DM). However, for select patients, clinical islet transplantation is an alternative therapeutic treatment. In this procedure, islets are transplanted into the hepatic portal vein, and despite improved success within the last decade, obstacles are still associated with this approach. It has been discovered that the subcutaneous space may be an effective alternative site for islet transplantation, and may provide advantages of easy access and potential for simple monitoring. The ability to monitor islet viability and the transplant microenvironment may be key to future success in islet transplantation. A subcutaneous device-less technique has been developed to facilitate angiogenesis in the islet transplant site, however, a method for monitoring the potential engraftment site have yet to be explored fully. Here we demonstrate the ability to track angiogenesis in mice with 1, 2, 3 and 4 weeks post-catheter implant on both sides of the abdomen using a FujiFilm VisualSonics Vevo-LAZR system. Quantitative analysis on vessel densities exhibited gradual vessel growth successfully induced by catheter implantation. Our study demonstrates the ability of employing photoacoustic and micro-ultrasound imaging to track angiogenesis around the catheter site prior to islet transplantation.

Use of micro-CT-based finite element analysis to accurately quantify peri-implant bone strains: a validation in rat tibiae.

PubMed

Torcasio, Antonia; Zhang, Xiaolei; Van Oosterwyck, Hans; Duyck, Joke; van Lenthe, G Harry

2012-05-01

Although research has been addressed at investigating the effect of specific loading regimes on bone response around the implant, a precise quantitative understanding of the local mechanical response close to the implant site is still lacking. This study was aimed at validating micro-CT-based finite element (μFE) models to assess tissue strains after implant placement in a rat tibia. Small implants were inserted at the medio-proximal site of 8 rat tibiae. The limbs were subjected to axial compression loading; strain close to the implant was measured by means of strain gauges. Specimen-specific μFE models were created and analyzed. For each specimen, 4 different models were created corresponding to different representations of the bone-implant interface: bone and implant were assumed fully osseointegrated (A); a low stiffness interface zone was assumed with thickness of 40 μm (B), 80 μm (C), and 160 μm (D). In all cases, measured and computational strains correlated highly (R (2) = 0.95, 0.92, 0.93, and 0.95 in A, B, C, and D, respectively). The averaged calculated strains were 1.69, 1.34, and 1.15 times higher than the measured strains for A, B, and C, respectively, and lower than the experimental strains for D (factor = 0.91). In conclusion, we demonstrated that specimen-specific FE analyses provide accurate estimates of peri-implant bone strains in the rat tibia loading model. Further investigations of the bone-implant interface are needed to quantify implant osseointegration.

Bronchocarcinogenic properties of welding and thermal spraying fumes containing chromium in the rat.

PubMed

Berg, N O; Berlin, M; Bohgard, M; Rudell, B; Schütz, A; Warvinge, K

1987-01-01

The possible bronchocarcinogenic effects of fumes released during the shielded metal arc welding of stainless steel and the thermal spraying of chromium oxide (Cr2O3) have been studied on the rat. The fume particles were shown to contain tri- and hexavalent chromium in soluble and low soluble forms; they were collected and implanted as pellets in the bronchi of groups of 100 rats by the method of Laskin et al. A negative control group of 100 rats was included, as well as positive controls receiving pellets containing benz(a)pyrene. The experiment was continued for 34 months; no differences of biological significance were noted between the growth rates, survival times, and terminal organ weights of the test and negative control groups. At autopsy, the macroscopic and microscopic appearance of the organs in the three groups, including the local reaction to the implanted pellet, were similar. No precancerous changes were observed at the implantation sites; one rat, who received a pellet containing welding fumes, showed squamous cell carcinoma remote from the implantation site and not associated with the bronchus. It had the appearance of a metastasis. All three benz(a)pyrene control rats developed cancer at the implantation site. The occupational health implications of these findings are discussed.

Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

NASA Astrophysics Data System (ADS)

Sato, Yoshinori; Yokoyama, Atsuro; Nodasaka, Yoshinobu; Kohgo, Takao; Motomiya, Kenichi; Matsumoto, Hiroaki; Nakazawa, Eiko; Numata, Tomoko; Zhang, Minfang; Yudasaka, Masako; Hara, Hideyuki; Araki, Rikita; Tsukamoto, Osamu; Saito, Hiroaki; Kamino, Takeo; Watari, Fumio; Tohji, Kazuyuki

2013-08-01

Because of their mechanical strength, chemical stability, and low molecular weight, carbon nanotubes (CNTs) are attractive biological implant materials. Biomaterials are typically implanted into subcutaneous tissue or bone; however, the long-term biopersistence of CNTs in these tissues is unknown. Here, tangled oxidized multi-walled CNTs (t-ox-MWCNTs) were implanted into rat subcutaneous tissues and structural changes in the t-ox-MWCNTs located inside and outside of macrophages were studied for 2 years post-implantation. The majority of the large agglomerates were present in the intercellular space, maintained a layered structure, and did not undergo degradation. By contrast, small agglomerates were found inside macrophages, where they were gradually degraded in lysosomes. None of the rats displayed symptoms of cancer or severe inflammatory reactions such as necrosis. These results indicate that t-ox-MWCNTs have high biopersistence and do not evoke adverse events in rat subcutaneous tissue in vivo, demonstrating their potential utility as implantable biomaterials.

Basal forebrain infusion of HC-3 in rats: maze learning deficits and neuropathology.

PubMed

Hurlbut, B J; Lubar, J F; Switzer, R; Dougherty, J; Eisenstadt, M L

1987-01-01

Ten adult male Sprague-Dawley rats were infused with hemicholinium (HC-3) using mini-osmotic pumps over a 14 day period through bilateral, chronically implanted cannulae in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline. HC-3 rats receiving implants demonstrated a significant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannulae were located within infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary damage were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.

Ectopic bone formation in nude rats using human osteoblasts seeded poly(3)hydroxybutyrate embroidery and hydroxyapatite-collagen tapes constructs.

PubMed

Mai, Ronald; Hagedorn, Manolo Gunnar; Gelinsky, Michael; Werner, Carsten; Turhani, Dritan; Späth, Heike; Gedrange, Tomas; Lauer, Günter

2006-09-01

The aim of this study was to evaluate the ectopic bone formation using tissue engineered cell-seeded constructs with two different scaffolds and primary human maxillary osteoblasts in nude rats over an implantation period of up to 96 days. Collagen I-coated Poly(3)hydroxybutyrate (PHB) embroidery and hydroxyapatite (HAP) collagen tapes were seeded with primary human maxillary osteoblasts (hOB) and implanted into athymic rnu/run rats. A total of 72 implants were placed into the back muscles of 18 rats. 24, 48 and 96 days after implantation, histological and histomorphometric analyses were made. The osteoblastic character of the cells was confirmed by immunocytochemistry and RT-PCR for osteocalcin. Histological analysis demonstrated that all cell-seeded constructs induced ectopic bone formation after 24, 48 and 96 days of implantation. There was more mineralized tissue in PHB constructs than in HAP-collagen tapes (at day 24; p < 0.05). Bone formation decreased with the increasing length of the implantation period. Osteocalcin expression verified the osteoblastic character of the cell-seeded constructs after implantation time. No bone formation and no osteocalcin expression were found in the control groups. Cell-seeded constructs either with PHB embroidery or HAP-collagen tapes can induce ectopic bone formation. However, the amount of bone formed decreased with increasing length of implantation.

Strontium enhances osseointegration of calcium phosphate cement: a histomorphometric pilot study in ovariectomized rats.

PubMed

Baier, Martin; Staudt, Patric; Klein, Roman; Sommer, Ulrike; Wenz, Robert; Grafe, Ingo; Meeder, Peter Jürgen; Nawroth, Peter P; Kasperk, Christian

2013-06-07

Calcium phosphate cements are used frequently in orthopedic and dental surgeries. Strontium-containing drugs serve as systemic osteoblast-activating medication in various clinical settings promoting mechanical stability of the osteoporotic bone. Strontium-containing calcium phosphate cement (SPC) and calcium phosphate cement (CPC) were compared regarding their local and systemic effects on bone tissue in a standard animal model for osteoporotic bone. A bone defect was created in the distal femoral metaphysis of 60 ovariectomized Sprague-Dawley rats. CPC and SPC were used to fill the defects in 30 rats in each group. Local effects were assessed by histomorphometry at the implant site. Systemic effects were assessed by bone mineral density (BMD) measurements at the contralateral femur and the spine. Faster osseointegration and more new bone formation were found for SPC as compared to CPC implant sites. SPC implants exhibited more cracks than CPC implants, allowing more bone formation within the implant. Contralateral femur BMD and spine BMD did not differ significantly between the groups. The addition of strontium to calcium phosphate stimulates bone formation in and around the implant. Systemic release of strontium from the SPC implants did not lead to sufficiently high serum strontium levels to induce significant systemic effects on bone mass in this rat model.

Effect of acclimation to caging on nephrotoxic response of rats to uranium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Damon, E.G.; Eidson, A.F.; Hobbs, C.H.

1986-02-01

Animal studies of the toxicity and metabolism of radionuclides and chemicals often require housing of rats in metabolism cages for excreta collection. Response of rats to toxic substances may be affected by environmental factors such as the type of cage used. Dose-response studies were conducted to assess the effects of two types of cages on the nephrotoxic response of rats to uranium from implanted refined uranium ore (yellowcake). The LD50/21 days was 6 mg of uranium ore per kilogram body weight (6 mg U/kg). The 95% confidence limit (C.L.) was 3-8 mg U/kg for rats housed in metabolism cages beginningmore » on the day of implantation (naive rats). However, for rats housed in metabolism cages for 21 days before implantation (acclimated rats) the LD50/21 days was 360 mg U/kg (95% C.L. = 220-650 mg U/kg), which was the same value obtained for rats housed continuously in polycarbonate cages. This significant difference (P less than 0.01) in response of naive rats compared to response of acclimated rats appeared related to a significantly lower water consumption by the naive rats.« less

Effect of acclimation to caging on nephrotoxic response of rats to uranium.

PubMed

Damon, E G; Eidson, A F; Hobbs, C H; Hahn, F F

1986-02-01

Animal studies of the toxicity and metabolism of radionuclides and chemicals often require housing of rats in metabolism cages for excreta collection. Response of rats to toxic substances may be affected by environmental factors such as the type of cage used. Dose-response studies were conducted to assess the effects of two types of cages on the nephrotoxic response of rats to uranium from implanted refined uranium ore (yellowcake). The LD50/21 days was 6 mg of uranium ore per kilogram body weight (6 mg U/kg). The 95% confidence limit (C.L.) was 3-8 mg U/kg for rats housed in metabolism cages beginning on the day of implantation (naive rats). However, for rats housed in metabolism cages for 21 days before implantation (acclimated rats) the LD50/21 days was 360 mg U/kg (95% C.L. = 220-650 mg U/kg), which was the same value obtained for rats housed continuously in polycarbonate cages. This significant difference (P less than 0.01) in response of naive rats compared to response of acclimated rats appeared related to a significantly lower water consumption by the naive rats.

[Effect of low dose aspirin on osseointegration around titanium implants in osteoporotic rats].

PubMed

Yang, Q; Li, F L

2018-02-09

Objective: To investigate the effect of aspirin on osseointegration around titanium implants in ostoeporotic rats and to provide evidence for future researches and clinical application. Methods: A total of 60 female SD rats, aged 3-4 months, were divided into ovariectomy group (Ovx group, n= 48) and sham-ovariectomy group (Sham group, n= 12). The rats in Ovx group received ovariectomy and those in Sham group underwent sham-ovariectomy. Twelve weeks later, six rats in each group were randomly selected to confirm the osteoporosis models. The Ovx group was divided into 4 subgroups with 12 rats in each group, namely the osteoporosis group (OP group), and Aspirin groups (A1, A2, A3 group). Pure screw titanium implants were placed in the right tibia near metaphysis of all rats. Three days after implant surgery, aspirin groups were intragastrically administered aspirin at a dose of 2.06, 4.11, 8.21 mg·kg(-1)·d(-1) (A1, A2, A3), and OP group and Sham group were fed the same amount of normal saline. Four and 12 weeks following implantations surgery, half of the rats in each group were randomly chosen and sacrificed. Implant bone contact rate (IBCR), combined bone lamella width (CBLW) and trabercular width (TW) were observed and calculated using histomorphometric measurement. Results: Four weeks after implantations surgery, the TW and CBLW of rats in A1 group [(39.60±2.77) and (27.56±4.14) μm] and the IBCR, TW and CBLW of rats in A2 group and A3 group [A2: (47.21±4.19)%, (48.74±3.20) and (35.91±3.79) μm; A3: (47.35±6.07)%, (50.27±5.25) and (40.66±2.11) μm] were much higher than those in OP group [(33.89±7.17)%, (32.20±6.10) and (19.77±6.80) μm]( P< 0.05). In term of CBLW, there were no difference between A3 group and Sham group [(46.11±5.87) μm]( P> 0.05). Twelve weeks after implantations surgery, the IBCR and CBLW of rats in A1 group [ (85.86±3.64) %, (53.12±8.68) μm], and the IBCR, TW and CBLW of rats in A2 group and A3 group [A2: (85.64±3.97)%, (69.42±6.78) and (54.19±3.12) μm; A3: (86.22±3.48)%, (75.43±3.50) and (55.79±5.60) μm] were much higher than those in OP group [(77.20±7.14)%, (55.10±2.26) and (41.77±3.13) μm]( P< 0.05). In term of IBCR, there were no difference among A1 group, A2 group, A3 group and Sham group [(90.09±2.21)%]( P> 0.05). Conclusions: The low dose aspirin could promote IBCR, CBLW and TW of osteoporotic rats implants.

Pneumococcal meningitis: development of a new animal model

PubMed Central

Wei, Benjamin P.C.; Shepherd, Robert K.; Robins-Browne, Roy M.; Clark, Graeme M.; O’Leary, Stephen J.

2007-01-01

Hypothesis The rat is a suitable animal to establish a model for the study of pneumococcal meningitis post cochlear implantation Background There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis post implantation and are based on relatively small animal numbers, making it difficult to assess the cause and effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. Methods Eighteen non-implanted rats were infected with 1× 106 and 1 × 108 colony forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear and intraperitoneal) to examine for evidence of meningitis over 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 × 1010 CFU intraperitoneal, 3 × 108CFU middle ear, 1 × 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. Histological pattern of cochlear infections for each of the three different inoculating routes were examined. Results Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system either via the cochlear aqueduct or canaliculi perforantes of osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 non-implanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours post-inoculation. Conclusion Meningitis in implanted rats following inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 non-implanted rats suggests longer post-inoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work we have developed a new animal model that will allow quantitative risk assessment of meningitis post cochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies. PMID:16936571

Embryotoxicity and fetotoxicity following intraperitoneal administrations of hexavalent chromium to pregnant rats.

PubMed

Marouani, Neila; Tebourbi, Olfa; Mokni, Moncef; Yacoubi, Mohamed Tahar; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais

2011-08-01

Heavy metals are omnipresent in the environment, and industrial use has greatly increased their presence in soil, water and air. Their inevitable transfer to the human food chain remains an important environmental issue as many heavy metals cause a range of toxic effects, including developmental toxicity. Administration of chromium VI (1 and 2 mg/kg as potassium dichromate) through intraperitoneal (i.p.) injection during organogenesis (days 6 to 15 of gestation) in rats revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses per mother and high incidences of dead fetuses and resorptions in treated mothers were also observed. Gross morphological abnormalities, such as displayed form of edema, facial defect, lack of tail, hypotrophy, severs subdermal haemorrhage patches and hypotrophy of placenta were observed in fetuses after chromium VI-treated mothers. A skeletal development of fetuses presented an incomplete ossification in nasal, cranium, abdominal or caudal bones in rats treated with 1 mg/kg of chromium, whereas rats treated with 2 mg/kg showed ossification and absence of the sacral vertebrae compared with the control. At a higher dose of chromium, histological changes were found in fetuses with atrophy of theirs vital organs. Placental histological observations revealed a pronounced morphological alteration, with atrophy of decidual cells, a degenerated of chorionic villi and hypertrophy of blood lacuna. The present study suggests a risk to the developing embryo when the mother is exposed to a high concentration of chromium VI during organogenesis.

The para isomer of dinitrobenzene disrupts redox homeostasis in liver and kidney of male wistar rats.

PubMed

Sangodele, Janet Olayemi; Olaleye, Mary Tolulope; Monsees, Thomas K; Akinmoladun, Afolabi Clement

2017-07-01

Para - Dinitrobenzene (p -DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p -DNB. This study evaluated the effect of sub-chronic exposure of rats to p -DNB on cellular redox balance, hepatic and renal integrity. Forty eight male Wistar rats weighing 160-180 g were administered 50, 75, 1000 and 2000 mg/kg b.wt (body weight) of p -DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated. Compared with control animals, p -DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p -DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p -DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver. Our findings show that sub-chronic oral and sub-dermal administration of p -DNB may produce hepato-nephrotoxicity through oxidative stress.

Study of the boron levels in serum after implantation of different ratios nano-hexagonal boron nitride-hydroxy apatite in rat femurs.

PubMed

Atila, Alptug; Halici, Zekai; Cadirci, Elif; Karakus, Emre; Palabiyik, Saziye Sezin; Ay, Nuran; Bakan, Feray; Yilmaz, Sahin

2016-01-01

Boron and its derivatives are effective in bone recovery and osteointegration. However, increasing the boron levels in body liquids may cause toxicity. The aim of our study is to investigate serum boron levels using ICP-MS after implantation of different ratios of nano-hBN-HA composites in rat femurs. All rats were (n=126) divided into five experimental groups (n=24) and one healthy group (6 rats); healthy (Group1), femoral defect + %100 HA (Group2), femoral defect + %2.5 hBN + %97.5 HA (Group3), femoral defect + %5 hBN + %95 HA (Group4), femoral defect + %10 hBN + %90 HA (Group5), femoral defect + %100 hBN (Group6). The femoral defect was created in the distal femur (3mm drill-bit). Each implant group was divided into four different groups (n=24) also 6 rats sacrificed for each groups in one week intervals during four weeks. In our results; at 1, 2, 3, and 4 weeks after implantation near bone tissue, serum levels of boron were evaluated using ICP-MS. We demonstrated that neither short-term nor long-term implantation of hBN-HA composite resulted in statistically increased serum boron levels in experimental groups compared to healthy group. In conclusion, this study investigated the implant material produced form hBN-HA for the first time. Our data suggest that hBN is a new promising target for biomaterial and implant bioengineers. Copyright © 2015 Elsevier B.V. All rights reserved.

Biocompatibility and characteristics of chitosan/cellulose acetate microspheres for drug delivery

NASA Astrophysics Data System (ADS)

Zhou, Hui-Yun; Zhou, Dong-Ju; Zhang, Wei-Fen; Jiang, Ling-Juan; Li, Jun-Bo; Chen, Xi-Guang

2011-12-01

In this work, chitosan/cellulose acetate microspheres (CCAM) were prepared by the method of W/O/W emulsion with no toxic reagents. The microspheres were spherical, free flowing, and non-aggregated, which had a narrow size distribution. More than 90% of the microspheres had the diameter ranging from 200 to 280 μm. The hemolytic analysis indicated that CCAM was safe and had no hemolytic effect. The implanted CCAM did not produce any significant changes in the hematology of Sprague-Dawley (SD) rats, such as white blood cell, red blood cell, platelet, and the volume of hemoglobin. In addition, the levels of serum alanine aminotransferase, blood urea nitrogen, and creatinine had no obvious changes in SD rats implanted with CCAM, surger thread, or normal SD rats without any implantation. Thus, the CCAM had good blood compatibility and had no hepatotoxicity or renal toxicity to SD rats. Furthermore, CCAM with or without the model drug had good tissue compatibility with respect to the inflammatory reaction in SD rats and showed no significant difference from that of SD rats implanted with surgery thread. CCAM shows promise as a long-acting delivery system, which had good biocompatibility and biodegradability.

Contamination of the Surgical Field with Propionibacterium acnes in Primary Shoulder Arthroplasty.

PubMed

Falconer, Travis M; Baba, Mohammed; Kruse, Lisa M; Dorrestijn, Oscar; Donaldson, Matthew J; Smith, Margaret M; Figtree, Melanie C; Hudson, Bernard J; Cass, Benjamin; Young, Allan A

2016-10-19

Propionibacterium acnes is a common pathogen identified in postoperative shoulder infection. It has been shown to be present in culture specimens during primary shoulder arthroplasty; however, recent work has suggested that it is most likely to be a contaminant. Our aim was to identify the potential sources of contamination in shoulder arthroplasty. Tissue swabs were obtained for microbiological analysis from consecutive patients undergoing primary shoulder arthroplasty. Routine surgical technique was maintained, and 5 specimens were taken from different sites: (1) the subdermal layer, (2) the tip of the surgeon's glove, (3) the inside scalpel blade (used for deeper incision), (4) the forceps, and (5) the outside scalpel blade (used for the skin incision). Forty patients (25 female patients and 15 male patients) were included. Thirteen (33%) of the 40 patients had at least 1 culture specimen positive for P. acnes. Two (8%) of the 25 female patients and 11 (73%) of the 15 male patients had ≥1 culture specimen positive for P. acnes. The most common site of growth of P. acnes was the subdermal layer (12 positive samples), followed by the forceps (7 positive samples), the tip of the surgeon's glove (7 positive samples), the outside scalpel blade (4 positive samples), and the inside scalpel blade (1 positive sample). There were 27 of 75 swabs that were positive on culture for P. acnes in male patients compared with 4 of 125 swabs in female patients. Male patients had 66 times (95% confidence interval, 6 to 680 times) higher odds of having a positive culture indicating subdermal colonization compared with female patients (p < 0.001). P. acnes is a common contaminant of the surgical field in primary shoulder arthroplasty. The subdermal layer may be the source of this contamination, and the prevalence of P. acnes in the surgical wound may be due to the surgeon's manipulation with gloves and instruments. Our findings are consistent with those regarding the increased rates of P. acnes bacterial load and intraoperative growth in male patients compared with female patients. P. acnes is likely to be spread throughout the surgical field from the subdermal layer via soft-tissue handling by the surgeon and instruments. Strategies need to be utilized to minimize this contact and to reduce the chance of colonization. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

ASSESSMENT OF ESTROGENICITY BY USING THE DELAYED IMPLANTING RAT MODEL AND EXAMPLES

EPA Science Inventory

Assessment of estrogenicity by using the delayed implanting rat model and examples.

Cummings AM, Laws SC.

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, N...

Skeletal response to corticosteroid deficiency and excess in growing male rats

NASA Technical Reports Server (NTRS)

Li, M.; Shen, Y.; Halloran, B. P.; Baumann, B. D.; Miller, K.; Wronski, T. J.

1996-01-01

The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not affect cortical bone mass. The results indicate that corticosteroid deficiency induces cancellous osteopenia, whereas supplementation with a near physiologic dose of the hormone prevents this bone loss in ADX rats. Furthermore, corticosteroid excess inhibits bone growth and bone turnover in a dose-dependent manner, but does not induce cancellous osteopenia in growing male rats.

Effects of enviromental temperature and femoral fracture on wound healing in rats.

PubMed

Crowley, L V; Seifter, E; Kriss, P; Rettura, G; Nakao, K; Levenson, S M

1977-06-01

Femoral fracture, unilateral and bilateral, impaired the healing of dorsal skin incisions and formation of reparative granulation tissue in subcutaneously implanted polyvinyl alcohol sponges judged histologically and by breaking strengths and hydroxyproline contents, respectively, 1 week after injury in pair-fed rats kept at 22 degrees C. When rats were transferred to a room at 30 degrees C immediately after skin incision and sponge implants, with or without unilateral fracture, no differences in healing were observed between the two groups. Rats with skin incision, sponge implants, and either femoral fracture or sham-fracture excreted more urinary nitrogen than preoperatively when kept at 22 degrees. Counterpart groups transferred to a 30 degrees room right after operation excreted less urinary nitrogen than preoperatively, but because of lower food intakes postoperatively, the ratio of urinary nitrogen to food intake nitrogen was increased. With equivalent food intakes, pair-fed rats with fracture kept at 22 degrees postoperatively lost more weight and excreted more nitrogen than corresponding rats transfered to a 30 degrees room.

Gaps in monitoring systems for Implanon NXT services in South Africa: An assessment of 12 facilities in two districts

PubMed

Pillay, D; Morroni, C; Pleaner, M; Adeogba, O; Chersich, M; Naidoo, N; Mullick, S; Rees, H

2017-10-01

Background. Implanon NXT, a long-acting subdermal contraceptive implant, was introduced in South Africa (SA) in early 2014 as part of an expanded contraceptive method mix. After initial high levels of uptake, reports emerged of frequent early removals and declines in use. Monitoring of progress and challenges in implant service delivery could identify aspects of the programme that require strengthening. Objectives. To assess data management and record keeping within implant services at primary care facilities. Methods. We developed a checklist to assess the tools used for monitoring implant services and data reporting to district offices. The checklist was piloted in seven facilities. An additional six high-volume and six low-volume implant insertion clinics in the City of Johannesburg (CoJ), Gauteng Province, and the Dr Kenneth Kaunda District, North West Province, were selected for assessment. Results. All 12 facilities completed a Daily Head Count Register, which tallied the number of clients attending the clinic, but not information about implant use. A more detailed Tick Register recorded services that clinic attendees received, with nine documenting number of implant insertions and six implant removals. A more specific tool, an Insertion Checklist, collected data on insertion procedures and client characteristics, but was only used in CoJ (five of six facilities). Other registers, which were developed de novo by staff at individual facilities, captured more detailed information about insertions and removals, including reasons. Five of six low-volume insertion facilities used these registers, but only three of six high-volume facilities. No facilities used the form specifically developed by the National Department of Health for implant pharmacovigilance. Nine of 12 clinics reported data on numbers of insertions to the district office, six reported removals and none provided data on reasons for removals. Conclusion. For data to inform effective decision-making and quality improvement in implant services in SA, standardised reporting guidelines and data collection tools are needed, reinforced by staff training and quality assessment of data collection. Staff often took the initiative to fill gaps in reporting systems. Current systems are unable to accurately monitor uptake or discontinuation, or identify aspects of services requiring strengthening. Lack of pharmacovigilance data is especially concerning. Deficiencies noted in these monitoring systems may be common to family planning services more broadly, which warrants investigation. Creative Commons Attribution - NonCommercial Works License (CC BY-NC 4.0)

Dental caries induction in experimental animals by clinical strains of Streptococcus mutans isolated from Japanese children.

PubMed

Hamada, S; Ooshima, T; Torii, M; Imanishi, H; Masuda, N; Sobue, S; Kotani, S

1978-01-01

Oral implantation and the cariogenic activity of clinical strains of Streptococcus mutans which had been isolated from Japanese children and labeled with streptomycin-resistance were examined in specific pathogen-free Sprague-Dawley rats. All the seven strains tested were easily implanted and persisted during the experimental period. Extensive carious lesions were produced in rats inoculated with clinical strains of S. mutans belonging to serotypes c, d, e, and f, and maintained on caries-inducing diet no. 2000. Noninfected rats did not develop dental caries when fed diet no. 2000. Type d S. mutans preferentially induced smooth surface caries in the rats. Strains of other serotypes primarily developed caries of pit and fissure origin. Caries also developed in rats inoculated with reference S. mutans strains BHTR and FAIR (type b) that had been maintained in the laboratories for many years. However, the cariogenicity of the laboratory strains was found to have decreased markedly. All three S. sanguis strains could be implanted, but only one strain induced definite fissure caries. Two S. salivarius strains could not be implanted well in the rats and therefore they were not cariogenic. Four different species of lactobacilli also failed to induce dental caries in rats subjected to similar caries test regimen on diet no. 200. S. mutans strain MT6R (type c) also induce caries in golden hamsters and ICR mice, but of variable degrees.

Carcinogenicity and Immunotoxicity of Embedded Depleted Uranium and Heavy-Metal Tungsten Alloy in Rodents

DTIC Science & Technology

2006-10-01

the implantation site. In addition, WA-implanted rats (high-dose group) exhibited splenomegaly and hematological changes suggesting polycythemia ...controls. The hematological changes observed in the high-dose WA rats are suggestive of polycythemia . Cobalt has been used experimentally to induce... polycythemia in rats (Rakusan et al., 2001; Endoh et al., 2000) although the concentration required is far greater than found in the WA pellets. The

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.

PubMed

Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T

2014-11-01

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission. Published by Elsevier Ltd.

Histological Evaluation of the Biocompatibility of Polyurea Crosslinked Silica Aerogel Implants in a Rat Model: A Pilot Study

PubMed Central

Sabri, Firouzeh; Boughter Jr, John D.; Gerth, David; Skalli, Omar; Phung, Thien-Chuong N.; Tamula, George-Rudolph M.; Leventis, Nicholas

2012-01-01

Background Aerogels are a versatile group of nanostructured/nanoporous materials with physical and chemical properties that can be adjusted to suit the application of interest. In terms of biomedical applications, aerogels are particularly suitable for implants such as membranes, tissue growth scaffolds, and nerve regeneration and guidance inserts. The mesoporous nature of aerogels can also be used for diffusion based release of drugs that are loaded during the drying stage of the material. From the variety of aerogels polyurea crosslinked silica aerogels have the most potential for future biomedical applications and are explored here. Methodology This study assessed the short and long term biocompatibility of polyurea crosslinked silica aerogel implants in a Sprague-Dawley rat model. Implants were inserted at two different locations a) subcutaneously (SC), at the dorsum and b) intramuscularly (IM), between the gluteus maximus and biceps femoris of the left hind extremity. Nearby muscle and other internal organs were evaluated histologically for inflammation, tissue damage, fibrosis and movement (travel) of implant. Conclusion/Significance In general polyurea crosslinked silica aerogel (PCSA) was well tolerated as a subcutaneous and an intramuscular implant in the Sprague-Dawley rat with a maximum incubation time of twenty months. In some cases a thin fibrous capsule surrounded the aerogel implant and was interpreted as a normal response to foreign material. No noticeable toxicity was found in the tissues surrounding the implants nor in distant organs. Comparison was made with control rats without any implants inserted, and animals with suture material present. No obvious or noticeable changes were sustained by the implants at either location. Careful necropsy and tissue histology showed age-related changes only. An effective sterilization technique for PCSA implants as well as staining and sectioning protocol has been established. These studies further support the notion that silica-based aerogels could be useful as biomaterials. PMID:23251378

Histological evaluation of the biocompatibility of polyurea crosslinked silica aerogel implants in a rat model: a pilot study.

PubMed

Sabri, Firouzeh; Boughter, John D; Gerth, David; Skalli, Omar; Phung, Thien-Chuong N; Tamula, George-Rudolph M; Leventis, Nicholas

2012-01-01

Aerogels are a versatile group of nanostructured/nanoporous materials with physical and chemical properties that can be adjusted to suit the application of interest. In terms of biomedical applications, aerogels are particularly suitable for implants such as membranes, tissue growth scaffolds, and nerve regeneration and guidance inserts. The mesoporous nature of aerogels can also be used for diffusion based release of drugs that are loaded during the drying stage of the material. From the variety of aerogels polyurea crosslinked silica aerogels have the most potential for future biomedical applications and are explored here. This study assessed the short and long term biocompatibility of polyurea crosslinked silica aerogel implants in a Sprague-Dawley rat model. Implants were inserted at two different locations a) subcutaneously (SC), at the dorsum and b) intramuscularly (IM), between the gluteus maximus and biceps femoris of the left hind extremity. Nearby muscle and other internal organs were evaluated histologically for inflammation, tissue damage, fibrosis and movement (travel) of implant. In general polyurea crosslinked silica aerogel (PCSA) was well tolerated as a subcutaneous and an intramuscular implant in the Sprague-Dawley rat with a maximum incubation time of twenty months. In some cases a thin fibrous capsule surrounded the aerogel implant and was interpreted as a normal response to foreign material. No noticeable toxicity was found in the tissues surrounding the implants nor in distant organs. Comparison was made with control rats without any implants inserted, and animals with suture material present. No obvious or noticeable changes were sustained by the implants at either location. Careful necropsy and tissue histology showed age-related changes only. An effective sterilization technique for PCSA implants as well as staining and sectioning protocol has been established. These studies further support the notion that silica-based aerogels could be useful as biomaterials.

P2 porous titanium implants improve tendon healing in an acute rat supraspinatus repair model.

PubMed

Tucker, Jennica J; Gordon, Joshua A; Zanes, Robert C; Zuskov, Andrey; Vinciguerra, John D; Bloebaum, Roy D; Soslowsky, Louis J

2017-03-01

Current techniques in rotator cuff repair often lack structural integrity. P 2 porous titanium-coated constructs (DJO Surgical, Austin, TX, USA) promote osseointegration and soft tissue ingrowth. This study examined the ability of this material to improve the structural integrity of supraspinatus tendon repair in a rat model. We hypothesized that P 2 implants placed at the tendon-to-bone interface would improve mechanical and histologic measures of supraspinatus healing. Forty rats underwent supraspinatus repairs with P 2 implants in 1 shoulder and standard repair in the other. Rats were humanely killed at time 0 (n = 3), 2 weeks (n = 8), 4 weeks (n = 15), and 12 weeks (n = 14). Tendon-to-bone composite specimens were harvested and evaluated mechanically and histologically. Tendon cross-sectional area was decreased in the P 2 implant group at 4 weeks, percentage of relaxation was increased at 2 weeks, elastic modulus was increased at 4 weeks, and maximum load and maximum stress were both increased at 2 and 4 weeks. Histologic analysis revealed no foreign body reactions within or around the P 2 implant, and healthy viable bone was visible within the P 2 implant. The results support our hypothesis, specifically in early healing, in this randomized controlled animal study. These data support the use of P 2 porous titanium implants to improve tendon-to-bone healing. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Progesterone induces the growth and infiltration of human astrocytoma cells implanted in the cerebral cortex of the rat.

PubMed

Germán-Castelán, Liliana; Manjarrez-Marmolejo, Joaquín; González-Arenas, Aliesha; González-Morán, María Genoveva; Camacho-Arroyo, Ignacio

2014-01-01

Progesterone (P4) promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4 and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160  μ L), P4 (1 mg), RU486 (5 mg), or P4 + RU486 (1 mg and 5 mg, resp.) for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4 significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4 effects. All rats treated with P4 showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4 + RU486, respectively, presented it. Our data suggest that P4 promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor.

Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

PubMed Central

Germán-Castelán, Liliana; Manjarrez-Marmolejo, Joaquín; González-Arenas, Aliesha; González-Morán, María Genoveva; Camacho-Arroyo, Ignacio

2014-01-01

Progesterone (P4) promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4 and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL), P4 (1 mg), RU486 (5 mg), or P4 + RU486 (1 mg and 5 mg, resp.) for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4 significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4 effects. All rats treated with P4 showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4 + RU486, respectively, presented it. Our data suggest that P4 promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor. PMID:24982875

Long-term erythropoietin gene expression from transduced cells in bioisolator devices.

PubMed

Yanay, Ofer; Barry, Simon C; Flint, Lisa Y; Brzezinski, Margaret; Barton, Randall W; Osborne, William R A

2003-11-20

Recombinant erythropoietin (EPO) is widely administered for long-term treatment of anemia associated with renal failure and other chronic diseases. The ability to deliver EPO by gene therapy would have clinical and economic benefit. We compared autologous and allogeneic transduced primary vascular smooth muscle cells for their ability to provide sustained EPO gene expression when encapsulated in TheraCyte devices implanted subcutaneously (SQ) or intraperitoneally (IP) in rats. Cells were transduced with retrovirus vector LrEpSN encoding rat EPO cDNA. Rats that received either autologous or allogeneic transduced cells showed elevated hematocrits (HCTs) ranging from 50 to 79% that were sustained for more than 12 months. The HCT of control rats remained at baseline (45.8%). Rats that received second SQ implants of either autologous or allogeneic cells showed elevations in hematocrit that were sustained for up to 12 months, suggesting the absence of immunological responses to transduced cells or implant material. All experimental groups had statistically significant elevated HCT (p < 0.001) when compared with controls. Both SQ and IP implantation were equally effective in delivering EPO long term. There were no significant differences in white blood cell (WBC) or platelet (PLT) values between treated and control animals. Implantation of TheraCyte devices was well tolerated and histological evaluation of the devices up to 12 months after surgery revealed a high degree of vascularization and no evidence of host immune response. TheraCyte devices offer a simple and safe gene delivery system that provides sustained therapeutic gene expression, permit removal and implantation of new devices, and do not require immunosuppression of the host.

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

PubMed Central

Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

2016-01-01

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns. PMID:27210744

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

NASA Astrophysics Data System (ADS)

Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

2016-05-01

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.

Serum from ozone-exposed pregnant rats impairs viability and wound repair in trophoblasts in vitro

EPA Science Inventory

In our previous studies, ozone (O3) exposure during implantation [gestational day (GD) 5 and 6)] in rats resulted in intrauterine growth restriction (IUGR), suggesting impairment of implantation with exposure. The aim of this study was to (1) determine if serum collected from pre...

DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

EPA Science Inventory

Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

ABSTRACT
Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

Time Course of Peri-Implant Bone Regeneration around Loaded and Unloaded Implants in a Rat Model

PubMed Central

Jariwala, Shailly H.; Wee, Hwabok; Roush, Evan P.; Whitcomb, Tiffany L.; Murter, Christopher; Kozlansky, Gery; Lakhtakia, Akhlesh; Kunselman, Allen R.; Donahue, Henry J.; Armstrong, April D.; Lewis, Gregory S.

2018-01-01

The time-course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium-coated polyether-ether ketone (PEEK) implants on osseointegration using time-lapsed, non-invasive, in vivo micro-computed tomography (micro-CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague-Dawley rats. External cyclic loading (60 μm or 100 μm displacement, 1 Hz, 60 seconds) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high-resolution micro-CT (12.5 μm voxel size) at 2, 5, 9, and 12 days post-surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone-formation rate (BFR) and bone-resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 ± 10.0 % and 37.2 ± 10.0 %, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119 % increase in pull-out strength was measured in the loaded implants. PMID:27381807

Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats.

PubMed

Halliday, Amy J; Campbell, Toni E; Nelson, Timothy S; McLean, Karen J; Wallace, Gordon G; Cook, Mark J

2013-01-01

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site. Copyright © 2012 Elsevier Ltd. All rights reserved.

Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

NASA Technical Reports Server (NTRS)

Ronca, A. E.; Baer, L. A.; Wade, C. E.

2003-01-01

Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

Effects of Low-Intensity Pulsed Ultrasound on Implant Osseointegration in Ovariectomized Rats.

PubMed

Zhou, Hongbo; Hou, Yongfu; Zhu, Zhimin; Xiao, Weixiong; Xu, Qian; Li, Lei; Li, Xin; Chen, Wenchuan

2016-04-01

To investigate the effect of low-intensity pulsed ultrasound (US) on peri-implant bone healing and osseointegration under osteoporotic conditions. Seventy-two 12-week-old female Sprague Dawley rats received bilateral ovariectomies. Twelve weeks later, titanium implants were bilaterally placed in the proximal tibial metaphysis. The right tibia was exposed to low-intensity pulsed US (40 mW/cm 2 , spatial and temporal average) for 20 min/d starting the 2nd day after implantation, and the left tibia served as a control without stimulation. The rats were randomly assigned to 6 groups of 12 each according to the US duration (group 1: weeks 0-2, 280 minutes; group 2: weeks 0-4, 560 minutes; group 3: weeks 0-6, 840 minutes; group 4: weeks 0-8, 1120 minutes; group 5: weeks 0-10, 1400 minutes; group 6: weeks 0-12, 1680 minutes). At the end of the 2nd, 4th, 6th, 8th, 10th, and 12th weeks, the rats were euthanized, and bilateral tibias were harvested. Peri-implant bone volume and bone-implant contact were assessed by micro-computed tomography; the implant-bone interface was assessed histologically; and implant fixation strength was determined by a removal torque test. Low-intensity pulsed US increased bone-implant contact at the 4th, 6th, 8th, 10th, and 12th weeks (P = .019, .017, <.001, <.001, and <.001, respectively) and peri-implant bone volume at all times (P = <.001, .002, .012, .007, .005, and .010). Removal torque on the US side was improved at the 6th, 8th, 10th, and 12th weeks (P= .012, <.001, .006, and .009). Ultrasound evoked a favorable bone response in the histologic study. Low-intensity pulsed US might enhance new bone formation, especially at an early stage, and improve osseointegration in osteoporotic bone as an auxiliary method. However, further studies are needed to elucidate the mechanisms underlying its action. © 2016 by the American Institute of Ultrasound in Medicine.

Evaluation of the effect of implanted depleted uranium on male reproductive success, sperm concentration, and sperm velocity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arfsten, Darryl P.; Schaeffer, David J.; Johnson, Eric W.

Depleted uranium (DU) projectiles have been used in battle in Iraq and the Balkans and will continue to be a significant armor-penetrating munition for the US military. As demonstrated in the Persian Gulf War, battle injury from DU projectiles and shrapnel is a possibility, and removal of embedded DU fragments from the body is not always practical because of their location in the body or their small size. Previous studies in rodents have demonstrated that implanted DU mobilizes and translocates to the gonads, and natural uranium may be toxic to spermatazoa and the male reproductive tract. In this study, themore » effects of implanted DU pellets on sperm concentration, motility, and male reproductive success were evaluated in adult (P1) Sprague-Dawley rats implanted with 0, 12, or 20, DU pellets of 1x2 mm or 12 or 20 tantalum (Ta) steel pellets of 1x2 mm. Twenty DU pellets of 1x2 mm (760 mg) implanted in a 500-g rat are equal to approximately 0.2 pound of DU in a 154-lb (70-kg) person. Urinary analysis found that male rats implanted with DU were excreting uranium at postimplantation days 27 and 117 with the amount dependent on dose. No deaths or evidence of toxicity occurred in P1 males over the 150-day postimplantation study period. When assessed at postimplantation day 150, the concentration, motion, and velocity of sperm isolated from DU-implanted animals were not significantly different from those of sham surgery controls. Velocity and motion of sperm isolated from rats treated with the positive control compound {alpha}-chlorohydrin were significantly reduced compared with sham surgery controls. There was no evidence of a detrimental effect of DU implantation on mating success at 30-45 days and 120-145 days postimplantation. The results of this study suggest that implantation of up to 20 DU pellets of 1x2 mm in rats for approximately 21% of their adult lifespan does not have an adverse impact on male reproductive success, sperm concentration, or sperm velocity.« less

Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

PubMed

Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

2015-11-01

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P < 0.05) and sustained (1-2 months) decreased number of ICMS-defined jaw and tongue sites within face-M1 and -S1, and increased thresholds of ICMS-evoked responses in these sites. Furthermore, dental implant placement reversed the extraction-induced changes in face-S1, and in face-M1 the number of jaw sites even increased as compared to naive rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

Effects of Lidocaine, Bupivacaine, and Ropivacaine on Calcitonin Gene-Related Peptide and Substance P Levels in the Incised Rat Skin.

PubMed

Lapin, Guilherme A F; Hochman, Bernardo; Maximino, Jessica R; Chadi, Gerson; Ferreira, Lydia M

2016-04-01

To evaluate the effect of 2% lidocaine, 0.5% bupivacaine, and 0.75% ropivacaine on the release of substance P (SP) and calcitonin gene-related peptide (CGRP) in skin wounds. A primary, experimental, analytical, prospective, self-controlled, blinded study. The study is set in a university research center. Twenty-eight Wistar rats were randomly divided into 4 groups: lidocaine, bupivacaine, ropivacaine, and the control. After general anesthesia, a local anesthetic or 0.9% saline (control) was injected subdermally along a 2-cm line on the dorsal midline of each rat; 30 minutes later, an incision (nociceptive stimulus) was made along this line. The animals were euthanized, and skin samples were collected from the center of the incision line and sent for CGRP and SP quantification. Quantification of CGRP and SP by Western blotting. Substance P levels were similar in the lidocaine and ropivacaine groups but were significantly lower than those of the control group (P = .002); no significant difference in SP levels was found between the bupivacaine and control groups. Procalcitonin gene-related peptide levels were significantly lower in the experimental groups than those in control subjects (P = .009), with no significant differences among the experimental groups. No significant differences in CGRP levels were found among all groups. Lidocaine and ropivacaine inhibited SP release. All 3 local anesthetics inhibited the release of procalcitonin gene-related peptide, but not the release of CGRP in rat skin. Lidocaine and ropivacaine may inhibit neurogenic inflammation by biochemical pathways activated by SP, whereas bupivacaine seems to have no influence on this process.

Dura covered with fibrin glue reduces adhesions in abdominal wall defects.

PubMed

Schier, F; Srour, N; Waldschmidt, J

1991-12-01

Dura can greatly facilitate the closure of abdominal wall defects. However, a main disadvantage of its use are the adhesions which develop between omentum, bowel and dura and may lead to bowel obstructions. In this study various groups of rats had either the anterior wall replaced by untreated dura or by dura covered with fibrin glue prior to implantation. Adhesions were found in 75% of sham operated rats, 100% after untreated dura implantation and 50% after the implantation of fibrin glue treated dura.

Utilizing a Rat Delayed Implantation Model to Teach Integrative Endocrinology and Reproductive Biology

ERIC Educational Resources Information Center

Geisert, Rodney D.; Smith, Michael F.; Schmelzle, Amanda L.; Green, Jonathan A.

2018-01-01

In this teaching laboratory, the students are directed in an exercise that involves designing and performing an experiment to determine estrogen's role in regulating delayed implantation (diapause) in female rats. To encourage active participation by the students, a discussion question is provided before the laboratory exercise in which each…

Effect of Resorbable Collagen Plug on Bone Regeneration in Rat Critical-Size Defect Model.

PubMed

Liu, Weiqing; Kang, Ning; Dong, Yuliang; Guo, Yuchen; Zhao, Dan; Zhang, Shiwen; Zhou, Liyan; Seriwatanachai, Dutmanee; Liang, Xing; Yuan, Quan

2016-04-01

The purpose of this investigation was to examine the effect of resorbable collagen plug (RCP) on bone regeneration in rat calvarial critical-size defects. About 5-mm-diameter calvarial defects were created in forty 12-week-old male Sprague-Dawley rats and implanted with or without RCP. Animals were killed at 1, 2, 4, and 8 weeks postoperatively. After being killed, specimens were collected and subjected to micro-computed tomography (μCT) and histological analysis. The μCT showed a significant increase of newly formed bone volume/tissue volume in RCP-implanted defect compared with controls at all designated time points. After 8 weeks, the defects implanted with RCP displayed almost complete closure. Hematoxylin and eosin staining of the decalcified sections confirmed these observations and evidenced active bone regeneration in the RCP group. In addition, Masson's trichrome staining demonstrated that RCP implantation accelerated the process of collagen maturation. The RCP enhances bone regeneration in rat critical-size cranial defects, which suggest it might be a desired material for bone defect repair.

Perioperative alendronate, risedronate, calcitonin and indomethacin treatment alters femoral stem fixation and periprosthetic bone mineral density in ovariectomized rats.

PubMed

Cankaya, Deniz; Tabak, Yalcin; Ozturk, Akif Muhtar; Gunay, Muhammed Cuneyd

2015-07-01

Many factors affect implant stability and periprosthetic bone mineral density (BMD) following total joint arthroplasty. We asked whether perioperative alendronate, risedronate, calcitonin and indomethacine administration altered (1) femoral stem shear strength and periprosthetic bone mineral density BMD in ovariectomized rats and (2) whether there were differences in the effect of these drugs. Thirty overiectomized rats were divided into five groups and implanted with intramedullary mini-cortical screws in the femur. Four groups were treated with alendronate, risedronate, salmon calcitonin and indomethacin for 4 weeks preoperatively and 8 weeks postoperatively. Although alendronate and risedronate increased the periprosthetic BMD more than calcitonin, they did not alter implant fixation compared to calcitonin. Indomethacin significantly decreased the BMD around the stem and implant stability compared to all other groups. This study showed that perioperative treatment with bisphosphonates and calcitonin improved the BMD around the stems and implant stability. Although bisphosphonates increased the BMD more than calcitonin, there was no difference in implant stability. Indomethacin markedly decreased the periprosthetic BMD and implant stability. The main clinical significance of our study was the finding about the need to strictly avoid long-term use of high-dose nonsteroidal antiinflammatory drugs for patients who have major joint arthritis and a previous history of arthroplasty.

Cannabis sativa smoke inhalation decreases bone filling around titanium implants: a histomorphometric study in rats.

PubMed

Nogueira-Filho, Getulio da R; Cadide, Tiago; Rosa, Bruno T; Neiva, Tiago G; Tunes, Roberto; Peruzzo, Daiane; Nociti, Francisco Humberto; César-Neto, João B

2008-12-01

Although the harmful effect of tobacco smoking on titanium implants has been documented, no studies have investigated the effects of cannabis sativa (marijuana) smoking. Thus, this study investigated whether marijuana smoke influences bone healing around titanium implants. Thirty Wistar rats were used. After anesthesia, the tibiae surface was exposed and 1 screw-shaped titanium implant was placed bilaterally. The animals were randomly assigned to one of the following groups: control (n = 15) and marijuana smoke inhalation (MSI) 8 min/d (n = 15). Urine samples were obtained to detect the presence of tetra-hidro-cannabinoid. After 60 days, the animals were killed. The degree of bone-to-implant contact and the bone area within the limits of the threads of the implant were measured in the cortical (zone A) and cancellous bone (zone B). Tetra-hidro-cannabinoid in urine was positive only for the rats of MSI group. Intergroup analysis did not indicate differences in zone A-cortical bone (P > 0.01), however, a negative effect of marijuana smoke (MSI group) was observed in zone B-cancellous bone for bone-to-implant contact and bone area (Student's t test, P < 0.01) values. Considering the limitations of the present study, the deleterious impact of cannabis sativa smoke on bone healing may represent a new concern for implant success/failure.

Effect of alpha-lipoic acid on endometrial implants in an experimental rat model.

PubMed

Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Özgür, Tümay; Bayraktar, Suphi

2017-10-01

To investigate the antioxidant and anti-inflammatory effects of alpha-lipoic acid (ALA) in the treatment of endometriosis in an experimental rat model by evaluating biochemical and histopathologic parameters. Experimental endometriosis was induced by the peritoneal implantation of autologous endometrial tissue. The rats were randomly divided into two groups with eight rats each. Group I was intraperitoneally administered ALA 100 mg/kg/day for 14 days. Group II was intraperitoneally administered saline solution at the same dosage and over the same period. Endometrial implant volume was measured in both groups both pre- and post-treatment. Tumor necrosis factor alpha (TNF-α) was measured in peritoneal fluid. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were assessed in serum. The implants were histopathologically evaluated. In the ALA group, the serum TOS and OSI levels, the endometrial implant volumes, the TNF-α levels in serum and peritoneal fluid, and the histopathologic scores were significantly lower compared to the control group (P < 0.05). Alpha-lipoic acid may have a therapeutic potential in the treatment of endometriosis due to its antioxidant and anti-inflammatory effects. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Functional assessment of hepatocytes after transplantation into rat spleen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woods, R.J.; Fuller, B.J.; Attenburrow, V.D.

1982-02-01

The retention of structural integrity and metabolic function by isolated hepatocytes after ectopic transplantation has been investigated in autografted rats. Rats were partially hepatectomized and isolated hepatocytes prepared from the excised liver lobes were implanted into their spleens. Histological examination of the spleens 7 or more weeks after implantation revealed aggregates of hepatocytes in the red pulp. Two tests of biochemical function were applied to the hepatocytes after transplantation. In the first the hepatobiliary imaging agent technetium-99m N-(N'-(2, 6-dimethylphenyl)carbamoylmethyl)iminodiacetic acid (99mTc HIDA), which was shown to be avidly taken up by isolated hepatocytes in vitro, was infused into the tailmore » veins of autograft and control rats. Radioactivity accumulating in the spleens of autografted rats was markedly greater than that in controls implanted with lethally damaged cells or in nontransplanted rats. In the second the presence of bilirubin metabolites was sought in autograft spleens after intravenous infusion of bilirubin. Both mono- and diglucuronides of bilirubin were recovered from the spleens of autograft rats but no conjugates were recovered from the spleens of unoperated controls. We conclude that after autotransplantation isolated hepatocytes retain their morphology and at least some of their functional activities.« less

IFATS Collection: Adipose-Derived Stromal Cells Improve the Foreign Body Response

PubMed Central

Prichard, Heather L.; Reichert, William; Klitzman, Bruce

2015-01-01

Many implanted devices fail due to the formation of an avascular capsule surrounding the device. Additionally, fat has long been known to promote healing and vascularization. The goals of this study were to identify potential mechanisms of the provascular actions of adipose-derived stromal cells (ASCs) and to improve implant biocompatibility. First, adult ASCs and fibroblasts from rats were attached to polyurethane and polystyrene in vitro and their cytokine secretion profile was analyzed. Secretion of vascular endothelial growth factor (VEGF) from ASCs was 10 –70 times higher than fibroblasts after 3 and 6 days. Next, polyurethane, bare and with cellular coatings, was implanted subcutaneously in rats. The fibrous capsule surrounding bare polyurethane implants was 17%–32% thicker and the amount of collagen was 27% greater than the capsule surrounding ASC-coated implants. Finally, the microvessel density adjacent to ASC-coated polyurethane was approximately 50%–80% higher than bare polyurethane. In summary, ASCs attached to polyurethane have a dramatically increased VEGF production compared with fibroblasts in vitro, and these cells also produce an increased microvessel density in the surrounding tissue when implanted subcutaneously in rats. PMID:18436858

Evaluation of borate bioactive glass scaffolds with different pore sizes in a rat subcutaneous implantation model.

PubMed

Deliormanli, Aylin M; Liu, Xin; Rahaman, Mohamed N

2014-01-01

Borate bioactive glass has been shown to convert faster and more completely to hydroxyapatite and enhance new bone formation in vivo when compared to silicate bioactive glass (such as 45S5 and 13-93 bioactive glass). In this work, the effects of the borate glass microstructure on its conversion to hydroxyapatite (HA) in vitro and its ability to support tissue ingrowth in a rat subcutaneous implantation model were investigated. Bioactive borate glass scaffolds, designated 13-93B3, with a grid-like microstructure and pore widths of 300, 600, and 900 µm were prepared by a robocasting technique. The scaffolds were implanted subcutaneously for 4 weeks in Sprague Dawley rats. Silicate 13-93 glass scaffolds with the same microstructure were used as the control. The conversion of the scaffolds to HA was studied as a function of immersion time in a simulated body fluid. Histology and scanning electron microscopy were used to evaluate conversion of the bioactive glass implants to hydroxyapatite, as well as tissue ingrowth and blood vessel formation in the implants. The pore size of the scaffolds was found to have little effect on tissue infiltration and angiogenesis after the 4-week implantation.

Vitamin E Phosphate Coating Stimulates Bone Deposition in Implant-related Infections in a Rat Model.

PubMed

Lovati, Arianna B; Bottagisio, Marta; Maraldi, Susanna; Violatto, Martina B; Bortolin, Monica; De Vecchi, Elena; Bigini, Paolo; Drago, Lorenzo; Romanò, Carlo L

2018-06-01

Implant-related infections are associated with impaired bone healing and osseointegration. In vitro antiadhesive and antibacterial properties and in vivo antiinflammatory effects protecting against bone loss of various formulations of vitamin E have been demonstrated in animal models. However, to the best of our knowledge, no in vivo studies have demonstrated the synergistic activity of vitamin E in preventing bacterial adhesion to orthopaedic implants, thus supporting the bone-implant integration. The purpose of this study was to test whether a vitamin E phosphate coating on titanium implants may be able to reduce (1) the bacterial colonization of prosthetic implants and (2) bone resorption and osteomyelitis in a rat model of Staphylococcus aureus-induced implant-related infection. Twelve rats were bilaterally injected in the femurs with S aureus UAMS-1-Xen40 and implanted with uncoated or vitamin E phosphate-coated titanium Kirschner wires without local or systemic antibiotic prophylaxis. Eight rats represented the uninfected control group. A few hours after surgery, two control and three infected animals died as a result of unexpected complications. With the remaining rats, we assessed the presence of bacterial contamination with qualitative bioluminescence imaging and Gram-positive staining and with quantitative bacterial count. Bone changes in terms of resorption and osteomyelitis were quantitatively analyzed through micro-CT (bone mineral density) and semiquantitatively through histologic scoring systems. Six weeks after implantation, we found only a mild decrease in bacterial count in coated versus uncoated implants (Ti versus controls: mean difference [MD], -3.705; 95% confidence interval [CI], -4.416 to -2.994; p < 0.001; TiVE versus controls: MD, -3.063; 95% CI, -3.672 to -2.454; p < 0.001), whereas micro-CT analysis showed a higher bone mineral density at the knee and femoral metaphysis in the vitamin E-treated group compared with uncoated implants (knee joint: MD, -11.88; 95% CI, -16.100 to -7.664; p < 0.001 and femoral metaphysis: MD, -19.87; 95% CI, -28.82 to -10.93; p < 0.001). We found decreased osteonecrosis (difference between medians, 1.5; 95% CI, 1-2; p < 0.002) in the infected group receiving the vitamin E-coated nails compared with the uncoated nails. These preliminary findings indicate that vitamin E phosphate implant coatings can exert a protective effect on bone deposition in a highly contaminated animal model of implant-related infection. The use of vitamin E coatings may open new perspectives for developing coatings that can limit septic loosening of infected implants with bacterial contamination. However, a deeper insight into the mechanism of action and the local release of vitamin E as a coating for orthopaedic implants is required to be used in clinics in the near future. Although this study cannot support the antimicrobial properties of vitamin E, promising results were obtained for bone-implant osseointegration. These preliminary results will require further in vivo investigations to optimize the host response in the presence of antibiotic prophylaxis.

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats.

PubMed

Imai, Hisanori; Misra, Gauri P; Wu, Linfeng; Janagam, Dileep R; Gardner, Thomas W; Lowe, Tao L

2015-12-01

Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

PubMed Central

Imai, Hisanori; Misra, Gauri P.; Wu, Linfeng; Janagam, Dileep R.; Gardner, Thomas W.; Lowe, Tao L.

2015-01-01

Purpose Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. Methods The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. Results The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. Conclusions The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia. PMID:26658505

Degradation of oxalate in rats implanted with immobilized oxalate oxidase.

PubMed

Raghavan, K G; Tarachand, U

1986-01-20

Accumulation of oxalate leads to hyperoxaluria and calcium oxalate nephrolithiasis in man. Since oxalate is a metabolic end product in mammals, the feasibility of its enzymic degradation has been tested in vivo in rats by administering exogenous oxalate oxidase. Oxalate oxidase, isolated from banana fruit peels, in its native form was found to be non-active at the physiological pH of the recipient animal. However, its functional viability in the recipient animal was ensured by its prior binding with ethylenemaleic anhydride, thus shifting its pH activity curve towards the alkaline range. Rats implanted with dialysis membrane capsules containing such immobilized oxalate oxidase in their peritoneal cavities effectively metabolized intraperitoneally injected [14C]oxalate as well as its precursor [14C]glyoxalate. The implantation of capsules containing coentrapped multienzyme preparations of oxalate oxidase, catalase and peroxidase led to a further degradation of administered [14C]oxalate in rats.

[Studies on the immunologic behavior of standardized virus-induced rat tumor after cryosurgical and surgical treatment].

PubMed

Jaeschock, R R

1976-01-01

The authors report on the behavior of a virus-induced tumor in the rat after cryosurgical and surgical treatment and re-implantation of different tumor suspensions. No specific "immune-cryothermic response" could be demonstrated. The principle of the lysis of the re-implantate lies in devitalizing the primary tumor.

Effects of Chinese Materia Medica-Fubao Danggui Jiao on experimental endometriosis.

PubMed

Sun, Xing; Chen, Lijue; Zeng, Fanbo

2011-01-01

The objective of this paper was to investigate the effects of a Chinese Materia Medica variant -Fubao Danggui Jiao (FDJ)-on experimental endometriosis. An endometriosis model was created by virtue of auto-transplantation of endometrial tissue onto rats' abdominal walls. The implants were allowed to grow for 30 days until the successful completion of the model. After that, forty endometriotic rats were randomly divided into four study groups and given different treatments: (1) negative control group (water, 2ml/kg, per os); (2) FDJ-A group (FDJ, 2ml/kg, per os); (3) FDJ-B group (FDJ, 4ml/kg, per os); (4) Danazol group (70mg/kg, per os). After 30 days with treatments, the volumes of endometriotic implants in each rat were measured. The implants and normal uterine horns were removed for routine histological examination. FDJ caused significant decreases in volumes of the surviving endometriotic implants, with two different doses having statistically equivalent effects. Upon histological examination, FDJ was observed to cause regression of epithelium and stroma of endometriotic implants. FDJ had revealed promising therapeutic effects on endometriosis.

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats.

PubMed

Jiang, Nan; Du, Pinggong; Qu, Weidong; Li, Lin; Liu, Zhonghao; Zhu, Songsong

For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP) treatment and TiO 2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM), atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO 2 -modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO 2 -modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and suppressed osteoclastogenesis with increased expression of OPG and decreased levels of RANKL. These promising results show that PRP treatment combined with a TiO 2 -nanomodified surface can improve titanium-implant biomechanical stability in ovariectomized rats, suggesting a beneficial effect to support the success of implants in osteoporotic bone.

The synergistic effect of TiO2 nanoporous modification and platelet-rich plasma treatment on titanium-implant stability in ovariectomized rats

PubMed Central

Jiang, Nan; Du, Pinggong; Qu, Weidong; Li, Lin; Liu, Zhonghao; Zhu, Songsong

2016-01-01

For several decades, titanium and its alloys have been commonly utilized for endosseous implantable materials, because of their good mechanical properties, chemical resistance, and biocompatibility. But associated low bone mass, wear and loss characteristics, and high coefficients of friction have limited their long-term stable performance, especially in certain abnormal bone-metabolism conditions, such as postmenopausal osteoporosis. In this study, we investigated the effects of platelet-rich plasma (PRP) treatment and TiO2 nanoporous modification on the stability of titanium implants in osteoporotic bone. After surface morphology, topographical structure, and chemical changes of implant surface had been detected by scanning electron microscopy (SEM), atomic force microscopy, contact-angle measurement, and X-ray diffraction, we firstly assessed in vivo the effect of PRP treatment on osseointegration of TiO2-modified implants in ovariectomized rats by microcomputed tomography examinations, histology, biomechanical testing, and SEM observation. Meanwhile, the potential molecular mechanism involved in peri-implant osseous enhancement was also determined by quantitative real-time polymerase chain reaction. The results showed that this TiO2-modified surface was able to lead to improve bone implant contact, while PRP treatment was able to increase the implant surrounding bone mass. The synergistic effect of both was able to enhance the terminal force of implants drastically in biomechanical testing. Compared with surface modification, PRP treatment promoted earlier osteogenesis with increased expression of the RUNX2 and COL1 genes and suppressed osteoclastogenesis with increased expression of OPG and decreased levels of RANKL. These promising results show that PRP treatment combined with a TiO2-nanomodified surface can improve titanium-implant biomechanical stability in ovariectomized rats, suggesting a beneficial effect to support the success of implants in osteoporotic bone. PMID:27695328

Goblet cell mucins as the selective barrier for the intestinal helminths: T-cell-independent alteration of goblet cell mucins by immunologically 'damaged' Nippostrongylus brasiliensis worms and its significance on the challenge infection with homologous and heterologous parasites.

PubMed Central

Ishikawa, N; Horii, Y; Oinuma, T; Suganuma, T; Nawa, Y

1994-01-01

The aim of this study was to examine the role of T cells on the alteration of terminal sugars of goblet cell mucins in the small intestinal mucosa of parasitized rats and to clarify the biological significance of the altered mucins in the mucosal defence against intestinal helminths. For this purpose, Nippostrongylus brasiliensis adult worms obtained from donor rats at 7 ('normal' worms) or 13 days ('damaged' worms) post-infection were implanted intraduodenally into euthymic and hypothymic (rnu/rnu) rats. Expulsion of implanted normal worms and associated goblet cell changes were extremely delayed in hypothymic recipients compared with euthymic recipients. In contrast, intraduodenally implanted damaged worms were expelled by day 5 regardless of the strains. Around the time of expulsion of implanted damaged worms, euthymic recipients showed both goblet cell hyperplasia and alteration of mucins, whereas hypothymic rats showed only the latter. Dexamethasone treatment completely abolished goblet cell changes of both strains of recipients. To clarify the importance of the constitutional changes of goblet cell mucins in mucosal defence, euthymic rats were primed by implantation of damaged worms to induce goblet cell changes, and then 3 or 5 days later they were challenged by implantation with normal worms. The results show that when goblet cell changes were induced by priming with damaged worms, recipient rats could completely prevent the establishment of normal worms. When hypothymic rats were primed and challenged in the same manner, a similar but slightly less preventive effect was observed. Such a protective effect of altered mucins seems to be selective because priming of euthymic rats with damaged N. brasiliensis did not affect the establishment of Strongyloides venezuelensis. These results suggest that: (1) once N. brasiliensis adult worms are 'damaged' by the host's T-cell-dependent immune mechanisms, they can induce alteration of sugar residues of goblet cell mucins via host-mediated, T-cell-independent processes; (2) the expression of such altered mucins is highly effective not only in causing expulsion of established damaged worms but also in preventing establishment of normal worms; and (3) the preventive effect of altered mucins is selective against parasite species. Images Figure 2 Figure 4 PMID:8206520

Reaction of the rat tissues to implantation of polyhydroxyalkanoate films and ultrafine fibers.

PubMed

Maiborodin, I V; Shevela, A I; Morozov, V V; Novikova, Ya V; Matveeva, V A; Drovosekov, M N; Barannik, M I

2013-01-01

The reaction of various tissues of rats to implantation of polyhydroxyalkanoate films and ultrafine fibers was studied by optic microscopy. Implantation of polyhydroxyalkanoate films into the abdominal cavity caused a peritoneal reaction, leading after 1 month to the formation of fibrous adhesions between polyhydroxyalkanoate and intestinal loops. Under the skin and in the muscle tissue polyhydroxyalkanoate films were encapsulated in a thick fibrous capsule. Implantation of polyhydroxyalkanoate ultrathin fibers led to formation of foreign body granulomas in all tissues with perifocal inflammation and sclerosis of the adjacent tissues. The polymer was fragmented in these granulomas and phagocytosed by macrophages with the formation of giant foreign body cells. Hence, polyhydroxyalkanoate materials implanted in vivo caused chronic granulomatous inflammatory reaction and were very slowly destroyed by macrophages.

Effects of pore size, implantation time and nano-surface properties on rat skin ingrowth into percutaneous porous titanium implants

PubMed Central

Farrell, Brad J.; Prilutsky, Boris I.; Ritter, Jana M.; Kelley, Sean; Popat, Ketul; Pitkin, Mark

2013-01-01

The main problem of percutaneous osseointegrated implants is poor skin-implant integration, which may cause infection. This study investigated the effects of pore size (Small, 40–100 microns and Large, 100–160 microns), nanotubular surface treatment (Nano), and duration of implantation (3 and 6 weeks) on skin ingrowth into porous titanium. Each implant type was percutaneously inserted in the back of 35 rats randomly assigned to 7 groups. Implant extrusion rate was measured weekly and skin ingrowth into implants was determined histologically after harvesting implants. It was found that all 3 types of implants demonstrated skin tissue ingrowth of over 30% (at week 3) and 50% (at weeks 4–6) of total implant porous area under the skin; longer implantation resulted in greater skin ingrowth (p<0.05). Only one case of infection was observed (infection rate 2.9%). Small and Nano groups showed the same implant extrusion rate which was lower than the Large group rate (0.06±0.01 vs. 0.16 ± 0.02 cm/week; p<0.05). Ingrowth area was comparable in the Small, Large and Nano implants. However, qualitatively, the Nano implants showed greatest cellular inhabitation within first three weeks. We concluded that percutaneous porous titanium implants allow for skin integration with the potential for a safe seal. PMID:23703928

Transcutaneous RF-Powered Implantable Minipump Driven by a Class-E Transmitter

PubMed Central

Moore, William H.; Holschneider, Daniel P.; Givrad, Tina K.

2007-01-01

We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the implant current in the volume of the primary coil reflected the variations of the estimated coupling coefficient between the two coils. The pump could be activated in-vivo, while accommodating the vertical and horizontal movements of the animal. Advantages of this design include a weight reduction for the implant, an operation independent from a finite power source, and a remote activation/deactivation. PMID:16916107

Transcutaneous RF-powered implantable minipump driven by a class-E transmitter.

PubMed

Moore, William H; Holschneider, Daniel P; Givrad, Tina K; Maarek, Jean-Michel I

2006-08-01

We describe the design and testing of an inductive coupling system used to power an implantable minipump for applications in ambulating rats. A 2 MHz class-E oscillator driver powered a coil transmitter wound around a 33-cm-diameter rat cage. A receiver coil, a filtered rectifier, and a voltage-sensitive switch powered the implant. The implant DC current at the center of the primary coil (5.1 V) exceeded the level required to activate the solenoid valve in the pump. The variations of the implant current in the volume of the primary coil reflected the variations of the estimated coupling coefficient between the two coils. The pump could be activated in-vivo, while accommodating the vertical and horizontal movements of the animal. Advantages of this design include a weight reduction for the implant, an operation independent from a finite power source, and a remote activation/deactivation.

Antidiuretic effect of morphine in the rat: tolerance and physical dependence.

PubMed Central

Huidobro, F

1978-01-01

1 Injection of rats with morphine or methadone, before they received a water load equivalent to 5% of their body weight, produced a dose-dependent antidiuretic effect. Following the antidiuresis, urine was eliminated with kinetics similar to control untreated rats. 2 The antidiuretic effect of morphine or methadone was blocked by naloxone administered before the opiate, or reversed when given after the opiate. 3 Rats implanted with morphine pellets developed a marked degree of tolerance to the antidiuretic effect of morphine. Tolerance was also obtained on injection of three daily doses of morphine or methadone over two days. 4 Withdrawal symptoms were precipitated by naloxone in rats implanted with pellets of morphine; under these conditions the animals showed a marked reduction in urine production as compared to naive rats. PMID:568501

Comparative Analysis of Structural Responses of Rat Subcutaneous Fat on the Implantation of Samples of Polymethyl Methacrylate with Hydrophobic and Hydrophilic Surface.

PubMed

Kudasova, E O; Vlasova, L F; Semenov, D E; Lushnikova, E L

2017-03-01

Morphological analysis of the subcutaneous fat was performed in rats after subcutaneous implantation of basic dental plastic materials with different hydrophobic and hydrophilic properties. It was shown that subcutaneous implantation of dental plastics with mostly hydrophobic surface and low biocompatibility induced destructive and inflammatory processes of various intensities, sometimes with allergic component; morphological signs of processes persisted for 6 weeks. Modification of basic plastics using glow-discharge plasma and enhancement of their hydrophilicity and biocompatibility significantly reduced the intensity of destructive and inflammatory processes and ensured more rapid (in 2 weeks) repair of the destroyed tissues with the formation of fibrous capsule around the implant.

In situ gelable interpenetrating double network hydrogel formulated from binary components: thiolated chitosan and oxidized dextran.

PubMed

Zhang, Hanwei; Qadeer, Aisha; Chen, Weiliam

2011-05-09

In situ gelable interpenetrating double-network hydrogels composed of thiolated chitosan (Chitosan-NAC) and oxidized dextran (Odex), completely devoid of potentially cytotoxic small molecule cross-linkers and that do not require complex maneuvers or catalysis, have been formulated. The interpenetrating network structure is created by Schiff base formations and disulfide bond inter-cross-linkings through exploiting the disparity of their reaction times. Compared with the autogelable thiolated chitosan hydrogels that typically require a relatively long time span for gelation to occur, the Odex/Chitosan-NAC composition solidifies rapidly and forms a well-developed 3D network in a short time span. Compared with typical hydrogels derived from natural materials, the Odex/Chitosan-NAC hydrogels are mechanically strong and resist degradation. The cytotoxicity potential of the hydrogels was determined by an in vitro viability assay using fibroblast as a model cell, and the results reveal that the hydrogels are noncytotoxic. In parallel, in vivo results from subdermal implantation in mice models demonstrate that this hydrogel is not only highly resistant to degradation but also induces very mild tissue response.

In situ Gelable Interpenetrating Double Network Hydrogel Formulated from Binary Components: Thiolated Chitosan and Oxidized Dextran

PubMed Central

Zhang, Hanwei; Qadeer, Aisha; Chen, Weiliam

2011-01-01

In situ gelable interpenetrating double network hydrogels composed of thiolated chitosan (Chitosan-NAC) and oxidized dextran (Odex), completely devoid of potentially cytotoxic small molecule crosslinkers and do not require complex maneuvers or catalysis, have been formulated. The interpenetrating network structure is created by Schiff base formations and disulfide bond inter-crosslinkings through exploiting the disparity of their reaction times. Compare to the auto-gelable thiolated chitosan hydrogels that typically require a relatively long time span for gelation to occur, the Odex/Chitosan-NAC composition solidifies rapidly and forms a well-developed three-dimensional network in a short time span. Compare to typical hydrogels derived from natural materials, the Odex/Chitosan-NAC hydrogels are mechanically strong and resist degradation. The cytotoxicity potential of the hydrogels was determined by an in vitro viability assay using fibroblast as a model cell and the results reveal that the hydrogels are non-cytotoxic. In parallel, in vivo results from subdermal implantation in mice models demonstrate that this hydrogel is not only highly resistant to degradation but also induces very mild tissue response. PMID:21410248

The brief life of Norplant® in Brazil: controversies and reassemblages between science, society and State.

PubMed

Pimentel, Ana Cristina de Lima; Jannotti, Cláudia Bonan; Gaudenzi, Paula; Teixeira, Luiz Antonio da Silva

2017-01-01

Norplant® is the brand name of the world's first registered subdermal hormonal contraceptive implant, developed by the laboratories of the Population Council, an international organisation working in the area of fertility and population growth. The article revisits the trajectory of this contraceptive in Brazil from its arrival through clinical trials to its eventual ban in 1986 by the Brazilian regulatory agency responsible for approving medications at the time. Its circulation generated controversies related to research practices, side effects and political uses of the drug as a birth control method. This article focuses its analysis on the divergences related to research practices. It uses a controversy analysis technique, reviewing the versions of those involved, investigating their understandings and the effects that this object generated in their networks. Norplant® provoked displacements and associations between civil society groups, State authorities, scientists and physicians, industry, pharmaceutical products, research procedures, bureaucratic instruments, and the female users of the contraceptives. Scientific styles of medical thought were shaken up and new forms of thinking about scientific autonomy began to be discussed in the country.

Family planning in the teen population.

PubMed

Hillard, P J

1993-12-01

As an increasing percentage of adolescents reach their sexual debut at younger ages, effective contraceptive methods, which will decrease the risks of unintended pregnancies and sexually transmitted diseases (STDs), become even more critical. Contraceptive methods which are less 'compliance-dependent', such as the implantable subdermal levonorgestrel and the injectable depot formulation of medroxyprogesterone acetate, are popular in adolescents but careful counseling before method selection and on-going counseling when side-effects are experienced are necessary and essential. The use of condoms to decrease the risks of STDs will continue to be important for adolescents, and it remains to be seen what impact the long-term methods will have on effective condom use. Adolescents' access to abortions when contraceptive methods fail, or when no method is used, is being challenged with state laws which mandate parental notification or permission. A greater knowledge about the option of emergency contraception could potentially lead to increased use of this method, particularly when the option of medications such as RU486 becomes available. The potential for a reduction in unintended pregnancies in adolescents, and a reduced need for abortions is a welcome prospect.

An animal model of effects of nicotine exposure on endometrial receptivity and embryo implantation in pregnancy.

PubMed

Akpak, Yaşam Kemal; Çekmez, Yasemin; Erdoğan Çakır, Aslı; Karaca, Nilay; Batmaz, Gonca; Gülşen, Serdar; Tuştaş Haberal, Esra

2017-12-01

This study aims at evaluating the endometrial receptivity in uterus of pregnant rats exposed to nicotine via examination of integrin expression by immunohistochemical effect. In this study, 16 healthy pregnant rats were divided into two groups of control and study groups each comprising eight rats. The rats randomised to study group were given a certain amount of nicotine before and during the pregnancy. Integrin expression was detected in uterus of all rats by immunohistochemical staining. The effect of nicotine exposure on embryo implantation and the endometrial receptivity were immunohistochemically and pathologically evaluated. Comparison of both groups revealed no difference in living, viable foetuses. Intensity and universality of immunohistochemical staining of Integrin β3 for endometrial epithelium and endometrial stroma were detected to be identical between the groups. No immunochemical effect was observed on integrin expression, which is a very important part of receptivity in an animal model created with pregnant rats that were transdermally exposed to nicotine. Our study demonstrated that the harmful effect of nicotine use before and pregnancy on implantation is limited at the level of integrin expression, in a dose-dependent manner and also by considering the method of administration.

Functional assessment of hepatocytes after transplantation into rat spleen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woods, R.J.; Fuller, B.J.; Attenburrow, V.D.

1982-02-01

The retention of structural integrity and metabolic function by isolated hepatocytes after ectopic transplantation has been investigated in autografted rats. Rats were partially hepatectomized and isolated hepatocytes prepared from the excised liver lobes were implanted into their spleens. Histological examination of the spleens 7 or more weeks after implantation revealed aggregates of hepatocytes in the red pulp. Two tests of biochemical function were applied to the hepatocytes after tranplantation. In the first the hepatobiliary imaging agent technetium-99m N-(N'-(2,6-dimethylphenyl)carbamoylmethyl)iminodiacetic acid (/sup 99//sup m/Tc HIDA), which was shown to be avidly taken up by isolated hepatocytes in vitro, was infused into themore » tail veins of autograft and control rats. Radioactivity accumulating in the spleens of autografted rats was markedly greater than that in controls implanted with lethally damaged cells or in nontransplanted rats. In the second the presence of bilirubin metabolites was sought in autograft spleens after intravenous infusion of bilirubin. Both mono- and diglucuronides of bilirubin were recovered from the spleens of autograft rats but no conjugates were recovered from the spleens of unoperated controls. We conclude that after autotransplantation isolated hepatocytes retain their morphology and at least some of their functional activities.« less

Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats.

PubMed

Rezazad, Maryam; Farokhi, Farah

2014-09-01

Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant statues (TAS), creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema.

Genome Wide assessment of Early Osseointegration in Implant-Adherent Cells

NASA Astrophysics Data System (ADS)

Thalji, Ghadeer N.

Objectives: To determine the molecular processes involved in osseointegration. Materials and methods: A structured literature review concerning in vitro and in vivo molecular assessment of osseointegration was performed. A rat and a human model were then used to identify the early molecular processes involved in osseointegration associated with a micro roughened and nanosurface superimposed featured implants. In the rat model, 32 titanium implants with surface topographies exhibiting a micro roughened (AT-II) and nanosurface superimposed featured implants (AT-I) were placed in the tibiae of 8 rats and subsequently harvested at 2 and 4 days after placement. Whereas in the human model, four titanium mini-implants with either a moderately roughened surface (TiOblast) or super-imposed nanoscale topography (Osseospeed) were placed in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole genome microarray using the Affymetrix 1.1 ST Array platform was used to describe the gene expression profiles that were differentially regulated by the implant surfaces. Results: The literature review provided evidence that particular topographic cues can be specifically integrated among the many extracellular signals received by the cell in its signal transduction network. In the rat model, functionally relevant categories related to ossification, skeletal system development, osteoblast differentiation, bone development and biomineral tissue development were upregulated and more prominent at AT-I compared to AT-II. In the human model, there were no significant differences when comparing the two-implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix, collagen fibril organization and angiogenesis were upregulated at both surfaces. Abundant upregulation of several differential markers of alternative activated macrophages was also observed. The biological processes involved with the inflammatory/immune response gene expression were concomitantly downregulated. Conclusions: The presence of micro-roughened and nanosurface features modulated in vivo bone response. This work confirms previous evaluations and further implicates modulation of the inflammatory/immune responses as a factor affecting the accrual of bone mass shortly after implant placement.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Treatment of osteoporosis with TheraCyte-encapsulated parathyroid cells: a study in a rat model.

PubMed

Chou, F-F; Huang, S-C; Chen, S-S; Wang, P-W; Huang, P-H; Lu, K-Y

2006-01-01

The purpose of this study was to evaluate parathyroid function at monthly intervals following the implantation of TheraCyte-encapsulated live human parathyroid cells into ovariectomized rats and to determine the effect on bone mineral density (BMD) 4 months after ovariectomy ( 3 months after implantation). Parathyroid tissues were obtained from patients undergoing surgery for secondary hyperparathyroidism. In total, 21 Sprague-Dawley rats divided randomly into three groups were subjected to one of three treatments: (1) implanted with TheraCyte A-encapsulated 4x10(6) live parathyroid cells; (2) implanted with TheraCyte B-encapsulated 4x10(5) live parathyroid cells; (3) a sham operation; the control group. Rats were ovariectomized 1 month prior to the implantation of the TheraCyte. Blood was drawn at the time of implantation and at monthly intervals thereafter for 3 months to check the levels of calcium, phosphorus and intact parathyroid hormone (iPTH). The BMD of the lumbar spine (L1-L5) and of the left femoral bone was measured with dual-energy-X-ray absorptiometry (DEXA) 1 month after ovariectomy and 3 months after implantation of the TheraCyte (4 months after ovariectomy). We found that the viability ratio of cryopreserved tissues was between 55 and 79% after thawing. In the control group, the BMD of the lumbar spine (L1-L5) had not decreased significantly (p=0.237) nor had the BMD of the left femoral bone increased significantly (p=0.063) 3 months after implantation. In the TheraCyte A group, the BMD of both the lumbar spine (p=0.018) and left femoral bone (p=0.018) had increased significantly 3 months after implantation. In the TheraCyte B group, the BMD of both the lumbar spine (p=0.017) and the left femoral bone (p=0.025) had also increased significantly 3 months after implantation. Serum iPTH levels were higher in the TheraCyte A group than in the TheraCyte B group (p=0.006), and higher in the TheraCyte B group than in the control group (p=0.040). Serum calcium levels were not significantly higher in the TheraCyte group A than in the TheraCyte B group or in the control group. Serum phosphorus levels were not significantly different between the TheraCyte A and TheraCyte B groups. Implantation of TheraCyte A-encapsulated 4x10(5) live parathyroid cells and TheraCyte B-encapsulated 4x10(6) cells can increase the BMD of ovariectomized rats within 3 months of implantation. Neither cause high serum calcium and low phosphorus concentrations.

Influence of bone marrow-derived mesenchymal stem cells pre-implantation differentiation approach on periodontal regeneration in vivo.

PubMed

Cai, Xinjie; Yang, Fang; Yan, Xiangzhen; Yang, Wanxun; Yu, Na; Oortgiesen, Daniel A W; Wang, Yining; Jansen, John A; Walboomers, X Frank

2015-04-01

The implantation of bone marrow-derived mesenchymal stem cells (MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal periodontal regeneration is still unknown. This in vivo study explored which differentiation approach is most suitable for periodontal regeneration. Mesenchymal stem cells were obtained from Fischer rats and seeded onto poly(lactic-co-glycolic acid)/poly(ɛ-caprolactone) electrospun scaffolds, and then pre-cultured under different in vitro conditions: (i) retention of multilineage differentiation potential; (ii) osteogenic differentiation approach; and (iii) chondrogenic differentiation approach. Subsequently, the cell-scaffold constructs were implanted into experimental periodontal defects of Fischer rats, with empty scaffolds as controls. After 6 weeks of implantation, histomorphometrical analyses were applied to evaluate the regenerated periodontal tissues. The chondrogenic differentiation approach showed regeneration of alveolar bone and ligament tissues. The retention of multilineage differentiation potential supported only ligament regeneration, while the osteogenic differentiation approach boosted alveolar bone regeneration. Chondrogenic differentiation of MSCs before implantation is a useful strategy for regeneration of alveolar bone and periodontal ligament, in the currently used rat model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators.

PubMed

Hassani, Faezeh Arab; Peh, Wendy Yen Xian; Gammad, Gil Gerald Lasam; Mogan, Roshini Priya; Ng, Tze Kiat; Kuo, Tricia Li Chuen; Ng, Lay Guat; Luu, Percy; Yen, Shih-Cheng; Lee, Chengkuo

2017-11-01

Underactive bladder or detrusor underactivity (DU) is defined as a reduction of contraction strength or duration of the bladder wall. Despite the serious healthcare implications of DU, there are limited solutions for affected individuals. A flexible 3D printed implantable device driven by shape memory alloys (SMA) actuators is presented here for the first time to physically contract the bladder to restore voluntary control of the bladder for individuals suffering from DU. This approach is used initially in benchtop experiments with a rubber balloon acting as a model for the rat bladder to verify its potential for voiding, and that the operating temperatures are safe for the eventual implantation of the device in a rat. The device is then implanted and tested on an anesthetized rat, and a voiding volume of more than 8% is successfully achieved for the SMA-based device without any surgical intervention or drug injection to relax the external sphincter.

Morphologic study of three collagen materials for body wall repair.

PubMed

Soiderer, Emily E; Lantz, Gary C; Kazacos, Evelyn A; Hodde, Jason P; Wiegand, Ryan E

2004-05-15

The search for ideal prostheses for body wall repair continues. Synthetic materials such as polypropylene mesh (PPM) are associated with healing complications. A porcine-derived collagen-based material (CBM), small intestinal submucosa (SIS), has been studied for body wall repair. Renal capsule matrix (RCM) and urinary bladder submucosa (UBS) are CBMs not previously evaluated in this application. This is the first implant study using RCM. Full-thickness muscle/fascia ventral abdominal wall defects were repaired with SIS, RCM, UBS, and PPM in rats with omentum and omentectomy. A random complete block design was used to allot implant type to each of 96 rats. Healing was evaluated at 4 and 8 weeks. Adhesion tenacity and surface area were scored. Implant site dimensions were measured at implantation and necropsy. Inflammation, vascularization, and fibrosis were histopathologically scored. Data were compared by analysis of variance (P < 0.05). PPM produced a granulomatous foreign body response in contrast to the organized healing of CBM implants. CBM mean scores were lower than PPM scores for adhesion tenacity, surface area, and inflammation at each follow-up time for rats with omentums (P < 0.02). The CBMs had less tenacity and inflammation than PPM at each follow-up time in omentectomy groups (P < 0.008). Wound contraction was greater for PPM (P < 0.0001) for all rats. RCM and UBS were similar to SIS invoking reduced inflammation, adhesion, and contraction compared to PPM. The fibrotic response to PPM was unique and more intense compared to CBMs. These CBM implants appear morphologically acceptable and warrant continued investigation.

Oxidative Stress Status and Placental Implications in Diabetic Rats Undergoing Swimming Exercise After Embryonic Implantation

PubMed Central

Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos

2015-01-01

The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control—nondiabetic sedentary rats, control exercised—nondiabetic exercised rats, diabetic—diabetic sedentary rats, and diabetic exercised—diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. PMID:25361551

Peri-implant bone formation and implant integration strength of peptide-modified p(AAM-co-EG/AAC) interpenetrating polymer network-coated titanium implants.

PubMed

Barber, Thomas A; Ho, James E; De Ranieri, Aladino; Virdi, Amarjit S; Sumner, Dale R; Healy, Kevin E

2007-02-01

Interpenetrating polymer networks (IPNs) of poly (acrylamide-co-ethylene glycol/acrylic acid) functionalized with an -Arg-Gly-Asp- (RGD) containing 15 amino acid peptides, derived from rat bone sialoprotein (bsp-RGD(15), were grafted to titanium implants in an effort to modulate bone formation in the peri-implant region in the rat femoral ablation model. Bone-implant contact (BIC) and bone formation within the medullary canal were determined using microcomputed tomography at 2 and 4 weeks postimplantation. BIC for bsp-RGD(15)-IPN implants was enhanced relative to hydroxyapatite tricalcium phosphate (HA-TCP) coated implants, but was similar to all other groups. Aggregate bone formation neither indicated a dose-dependent effect of bsp-RGD(15) nor a meaningful trend. Mechanical testing of implant fixation revealed that only the HA-TCP coated implants supported significant (>1 MPa) interfacial shear strength, despite exhibiting lower overall BIC, an indication that bone ingrowth into the rougher coating was the primary mode of implant fixation. While no evidence was found to support the hypothesis that bsp-RGD(15)-modified IPN coated implants significantly impacted bone-implant bonding, these results point to the lack of correlation between in vitro studies employing primary osteoblasts and in vivo wound healing in the peri-implant region. Copyright 2006 Wiley Periodicals, Inc.

Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

PubMed

Thomas, Biju B; Zhu, Danhong; Zhang, Li; Thomas, Padmaja B; Hu, Yuntao; Nazari, Hossein; Stefanini, Francisco; Falabella, Paulo; Clegg, Dennis O; Hinton, David R; Humayun, Mark S

2016-05-01

To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats.

PubMed

Diefenbeck, M; Schrader, C; Gras, F; Mückley, T; Schmidt, J; Zankovych, S; Bossert, J; Jandt, K D; Völpel, A; Sigusch, B W; Schubert, H; Bischoff, S; Pfister, W; Edel, B; Faucon, M; Finger, U

2016-09-01

Implant related infection is one of the most feared and devastating complication associated with the use of orthopaedic implant devices. Development of anti-infective surfaces is the main strategy to prevent implant contamination, biofilm formation and implant related osteomyelitis. A second concern in orthopaedics is insufficient osseointegration of uncemented implant devices. Recently, we reported on a macroporous titanium-oxide surface (bioactive TiOB) which increases osseointegration and implant fixation. To combine enhanced osseointegration and antibacterial function, the TiOB surfaces were, in addition, modified with a gentamicin coating. A rat osteomyelitis model with bilateral placement of titanium alloy implants was employed to analyse the prophylactic effect of gentamicin-sodiumdodecylsulfate (SDS) and gentamicin-tannic acid coatings in vivo. 20 rats were randomly assigned to four groups: (A) titanium alloy; PBS inoculum (negative control), (B) titanium alloy, Staphylococcus aureus inoculum (positive control), (C) bioactive TiOB with gentamicin-SDS and (D) bioactive TiOB plus gentamicin-tannic acid coating. Contamination of implants, bacterial load of bone powder and radiographic as well as histological signs of implant-related osteomyelitis were evaluated after four weeks. Gentamicin-SDS coating prevented implant contamination in 10 of 10 tibiae and gentamicin-tannic acid coating in 9 of 10 tibiae (infection prophylaxis rate 100% and 90% of cases, respectively). In Group (D) one implant showed colonisation of bacteria (swab of entry point and roll-out test positive for S. aureus). The interobserver reliability showed no difference in the histologic and radiographic osteomyelitis scores. In both gentamicin coated groups, a significant reduction of the histological osteomyelitis score (geometric mean values: C = 0.111 ± 0.023; D = 0.056 ± 0.006) compared to the positive control group (B: 0.244 ± 0.015; p < 0.05) was observed. The radiographic osteomyelitis scores confirmed these histological findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stone, J.P.; Holtsman, S.; Shellabarger, C.J.

Pellets containing 5 mg (/sup 3/H) diethylstilbestrol (DES) and 15 mg cholesterol were implanted S.C. in 84-day-old female Sprague-Dawley (S-D) and ACl rats. DES was released from the implanted pellets exponentially, and the release was not significantly different in S-D rats than in ACl rats. No mammary tumors developed in any treated or untreated S-D rats. In contrast, 90% of the DES-treated ACl rats developed mammary adenocarcinomas. A significant increase in the weight of the pituitary was noted in DES-treated ACl rats. The pituitarities of the treated ACl rats were 2 to 7 times as heavy as were controls, andmore » plasma prolactin levels were 10 to 40 times higher than in controls. In contrast, the pituitaries of treated S-D rats did not significantly increase in weight, and plasma prolactin levels were only 3 to 5 times higher than controls. The uteri of treated S-D rats were significantly heavier than those of control rats and contained large amounts of fluid. This effect was not seen in ACl rats. Although the release of DES from the implanted pellet was essentially the same in ACl and S-D rats, three distinctive strain differences in response to DES were noted: mammary adenocarcinomas were found only in treated ACl rats; pituitary prolactin-cell adenomas and associated elevated plasma prolactins levels were seen only in treated ACl rats; and pyometritis was induced only in treated S-D rats. Mammary adenocarcinomas and prolactin-cell adenoma responses in the treated ACl rats appear to be correlated with the increasing levels of plasma prolactin. This study demonstrates that the prolonged estrogen treatment of ACl and S-D female rats produces distinctly different mammary and pituitary neoplastic responses. This disparity in neoplastic responses appears to be reflected in the difference of degree to which the hypophysical prolactin cells are stimulated to grow and secrete hormone.« less

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

PubMed

Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

2014-07-01

To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal

PubMed Central

Núnez, Cristina; Zelei, Edina; Polyák, Ágnes; Milanés, M. Victoria

2013-01-01

Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15–30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls. PMID:23805290

Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.

PubMed

Raghavan, Shreya; Miyasaka, Eiichi A; Gilmont, Robert R; Somara, Sita; Teitelbaum, Daniel H; Bitar, Khalil N

2014-04-01

The internal anal sphincter (IAS) is a major contributing factor to pressure within the anal canal and is required for maintenance of rectoanal continence. IAS damage or weakening results in fecal incontinence. We have demonstrated that bioengineered, intrinsically innervated, human IAS tissue replacements possess key aspects of IAS physiology, such as the generation of spontaneous basal tone and contraction/relaxation in response to neurotransmitters. The objective of this study is to demonstrate the feasibility of implantation of bioengineered IAS constructs in the perianal region of athymic rats. Human IAS tissue constructs were bioengineered from isolated human IAS circular smooth muscle cells and human enteric neuronal progenitor cells. After maturation of the bioengineered constructs in culture, they were implanted operatively into the perianal region of athymic rats. Platelet-derived growth factor was delivered to the implanted constructs through a microosmotic pump. Implanted constructs were retrieved from the animals 4 weeks postimplantation. Animals tolerated the implantation well, and there were no early postoperative complications. Normal stooling was observed during the implantation period. At harvest, implanted constructs were adherent to the perirectal rat tissue and appeared healthy and pink. Immunohistochemical analysis revealed neovascularization. Implanted smooth muscle cells maintained contractile phenotype. Bioengineered constructs responded in vitro in a tissue chamber to neuronally evoked relaxation in response to electrical field stimulation and vasoactive intestinal peptide, indicating the preservation of neuronal networks. Our results indicate that bioengineered innervated IAS constructs can be used to augment IAS function in an animal model. This is a regenerative medicine based therapy for fecal incontinence that would directly address the dysfunction of the IAS muscle. Copyright © 2014 Mosby, Inc. All rights reserved.

Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats.

PubMed

Ardura, Juan A; Portal-Núñez, Sergio; Lozano, Daniel; Gutiérrez-Rojas, Irene; Sánchez-Salcedo, Sandra; López-Herradón, Ana; Mulero, Francisca; Villanueva-Peñacarrillo, María L; Vallet-Regí, María; Esbrit, Pedro

2016-08-01

Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and μ-computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016. © 2016 Wiley Periodicals, Inc.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

Aspirin and Clopidogrel Inhibit Aneurysm Healing after HydroCoil Implantation in External Carotid Artery Aneurysm Model.

PubMed

Zhang, Chao; Li, Peiliang; Xi, Guohua; Gemmete, Joseph J; Chaudhary, Neeraj; Thompson, B Gregory; Pandey, Aditya S

2016-11-01

To understand whether the use of antiplatelet agents leads to less intra-aneurismal tissue formation following coil implantation in a rat end-pouch external carotid artery (ECA) aneurysm model. End-pouch ECA aneurysms were created in adult rats and were then embedded with either platinum or HydroCoils. Rats were treated either with aspirin, clopidogrel, aspirin + clopidogrel, or saline for 2 weeks after coil implantation. At 2 weeks after coil implantation, rats were sacrificed and the aneurysm pouch was removed for histological and immunohistochemical analysis. A blinded single observer calculated the percentage of the organized area and the residual length of elastic lamina within the aneurysm. Student's t-test was used to compare data from image analysis between the different groups. Within the platinum group, the organized tissue area was not affected by antiplatelet administration (aspirin versus saline, P = .83; clopidogrel versus saline, P = .46; aspirin + clopidogrel versus saline, P = .54). For the HydroCoil group, the organized tissue area was significantly reduced (aspirin versus saline, P = .02; clopidogrel versus saline, P = .04; aspirin + clopidogrel versus saline, P = .02) in rats treated with antiplatelet agents; however, no difference (aspirin versus clopidogrel, P = .8; aspirin versus aspirin + clopidogrel, P = .3; clopidogrel versus aspirin + clopidogrel, P = .5) was found among type or combination of antiplatelets administered. HydroCoil-treated aneurysms had a similar number of macrophages compared to the platinum group (P = .3819); however, the HydroCoil group had significant suppression of macrophages in the groups treated with combined antiplatelets (P = .02). Following HydroCoil implantation, the area of organized tissue is diminished significantly in a rat end-pouch ECA aneurysm model treated with antiplatelets. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats

PubMed Central

Rezazad, Maryam; Farokhi, Farah

2014-01-01

Objective: Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Materials and Methods: Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant statues (TAS), creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. Results: After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. Conclusion: These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema. PMID:25386393

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan.

PubMed

Cakmak, Bulent; Cavusoglu, Turker; Ates, Utku; Meral, Ayfer; Nacar, Mehmet Can; Erbaş, Oytun

2015-04-01

Endometriosis is a common disease in women of reproductive age, and many different treatments have been developed, although none has provided a cure. In this study, the efficacy of losartan, an angiotensin II type 1 receptor blocker and an antiangiogenic and anti-inflammatory agent, on regression of experimental endometriotic implants in a rat model was investigated. Peritoneal endometriosis was surgically induced in 16 mature female Sprague-Dawley rats. The peritoneal endometriotic implant was confirmed after 28 days, and the animals were divided randomly into two groups. The control group (n = 8) was given 4 mL/day tap water by oral gavage, and the losartan group (n = 8) was given 20 mg/kg per day losartan p.o. We compared endometriotic implant size, extent and severity of adhesion, as well as plasma and peritoneal lavage fluid cytokine levels including vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, plasma inflammatory factor pentraxin-3 (PTX-3) and C-reactive protein (CRP) between the treatment groups. Mean surface endometriotic area, histological score of implants, adhesion formation, plasma VEGF, TNF, PTX-3 and CRP levels were significantly lower in the losartan group compared with control (P < 0.05). Furthermore, the peritoneal VEGF level was lower in the losartan group than in the control group (P < 0.001), but peritoneal TNF-α was similar in both groups (P > 0.05). Losartan suppressed the implant surface area of experimental endometriosis in rats and reduced the levels of plasma VEGF, TNF-α, PTX-3 and CRP. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Evaluation of Autologous Fascia Implantation With Controlled Release of Fibroblast Growth Factor for Recurrent Laryngeal Nerve Paralysis Due to Long-term Denervation.

PubMed

Nagai, Hiromi; Nishiyama, Koichiro; Seino, Yutomo; Tabata, Yasuhiko; Okamoto, Makito

2016-06-01

Paralyzed tissue due to long-term denervation is resistant to many treatments because it induces irreversible histological changes and disorders of deglutition or phonation. We sought to determine the effect of autologous transplantation of fascia into the vocal fold (ATFV) with controlled release of basic fibroblast growth factor (bFGF) on long-term unilateral vocal fold paralysis (UVFP). Unilateral recurrent laryngeal nerve (RLN) section was performed on 20 rats. Five rats were implanted with autologous fascia only (fascia group), and 10 rats were implanted with autologous fascia and a gelatin hydrogel sheet with 1 μg (1 μg bFGF + fascia group) or 0.1 μg (0.1 μg bFGF + fascia group) of bFGF 4 months after RLN section. We evaluated the normalized glottal gap and laryngeal volume and histological changes 3 months after implantation. The normalized glottal gap was significantly reduced in the 3 fascia implantation groups. Normalized laryngeal volume, fat volume, and lateral thyroarytenoid muscle volume were significantly increased in the 2 fascia implantation with bFGF groups. The ATFV with controlled release of bFGF repaired the glottal gap and laryngeal volume after RLN section and may reduce the occurrence of aspiration and hoarseness. We speculate that this treatment improves laryngeal function in long-term RLN denervation. © The Author(s) 2016.

Toxicity testing of urinary catheters.

PubMed

Talja, M; Andersson, L C; Ruutu, M; Alfthan, O

1985-10-01

The tissue toxicity of 23 urinary catheter batches (6 latex and 2 non-latex brands) was tested in vitro and in vivo. In vitro, a human T-cell leukemia line (JM) was cultured in the presence of different concentrations of eluates made from the catheters. The cytotoxicity of the eluates was assessed from their ability to inhibit DNA synthesis measured by incorporation of 3H-thymidine. In vivo, two methods were used. Strips of catheters were implanted into the rabbit dorsal muscle and pieces of catheters were implanted into the rat peritoneal cavity. After four days, the foreign body reaction, type of inflammation and necrosis were quantified macroscopically and by light microscopy. The results of the in vitro cytotoxicity test were correlated with those of in vivo methods. The rat peritoneal implantation test correlated better with the cell culture test (P less than 0.01) than with the rabbit muscle implantation test (P less than 0.05). Based on the clinical experience of urethral stricture complications caused by urinary catheters, catheters yielding eluate which at 30% dilution inhibited 50% DNA synthesis were regarded as toxic. According to this, the rabbit muscle implantation test was not reliable in testing the tissue toxicity of urinary catheters, while the cell culture test was quantitative and seemed to correlate with both the rat peritoneal implantation test and with the clinical complications observed.

Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle.

PubMed Central

Schuschke, D. A.; Reed, M. W.; Saari, J. T.; Olson, M. D.; Ackermann, D. M.; Miller, F. N.

1992-01-01

The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion. PMID:1280989

Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

PubMed

Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

2017-11-15

Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional transcriptomics landscape and neurotransmitter levels at the tumor implantation site/normal tissue, accompanied by increased inflammation (astrogliosis). Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Low-Intensity Pulsed Ultrasound on Implant Osseointegration in Ovariectomized Rats.

PubMed

Zhou, Hongbo; Hou, Yongfu; Zhu, Zhimin; Xiao, Weixiong; Xu, Qian; Li, Lei; Li, Xin; Chen, Wenchuan

2016-04-01

To investigate the effect of low-intensity pulsed ultrasound (US) on periimplant bone healing and osseointegration under osteoporotic conditions. Seventy-two 12-week-old female Sprague Dawley rats received bilateral ovariectomies. Twelve weeks later, titanium implants were bilaterally placed in the proximal tibial metaphysis. The right tibia was exposed to low-intensity pulsed US (40 mW/cm2, spatial and temporal average) for 20 min/d starting the 2nd day after implantation, and the left tibia served as a control without stimulation. The rats were randomly assigned to 6 groups of 12 each according to the US duration (group 1: weeks 0–2, 280 minutes; group 2: weeks 0–4, 560 minutes; group 3: weeks 0–6, 840 minutes; group 4: weeks 0–8, 1120 minutes; group 5: weeks 0–10, 1400 minutes; group 6: weeks 0–12, 1680 minutes). At the end of the 2nd, 4th, 6th, 8th, 10th, and 12th weeks, the rats were euthanized, and bilateral tibias were harvested. Peri-implant bone volume and bone-implant contact were assessed by micro–computed tomography; the implantbone interface was assessed histologically; and implant fixation strength was determined by a removal torque test. Low-intensity pulsed US increased bone-implant contact at the 4th, 6th, 8th, 10th, and 12th weeks (P = .019, .017, <.001, <.001, and <.001, respectively) and periimplant bone volume at all times (P = <.001, .002, .012, .007, .005, and .010). Removal torque on the US side was improved at the 6th, 8th, 10th, and 12th weeks (P= .012, <.001, .006, and .009). Ultrasound evoked a favorable bone response in the histologic study. Low-intensity pulsed US might enhance new bone formation, especially at an early stage, and improve osseointegration in osteoporotic bone as an auxiliary method. However, further studies are needed to elucidate the mechanisms underlying its action.

Mrz 2/579, a fast kinetic NMDA channel blocker, reduces the development of morphine tolerance in awake rats.

PubMed

Houghton, A K; Parsons, C G; Headley, P M

2001-04-01

The purpose of the present study was to investigate whether uncompetitive NMDA antagonists with fast channel blocking kinetics, which show fewer side effects in man than compounds such as ketamine, affect the development of tolerance to continuous exposure to morphine. Rats were trained on the Randall--Selitto apparatus before being implanted, under halothane anaesthesia, with primed mini-osmotic pumps (240 microl/day). Six rats were implanted with a vehicle filled pump, seven with a morphine filled pump (28.8 mg/kg/day), and eight with a pair of pumps, one containing morphine and the other Mrz 2/579, a new NMDA antagonist (40 mg/kg/day). A fourth group was implanted with a morphine filled pump followed 25 h later by a Mrz 2/579 filled pump. Paw withdrawal tests were undertaken immediately before, and at 2, 4, 6, 8, 10, 12, 24, 48 and 72 h after the first pump was implanted. Before pump implantation, withdrawal thresholds were 120+/-7 g (mean+/-SEM, n=30). Vehicle infusion had no effect on withdrawal thresholds, whereas morphine infusion increased them significantly at 2 and 4 h after pump implantation (+2 h: 208+/-14 g; P<0.001 vs. control). From 6 h the antinociception elicited by morphine declined progressively; at 10 h withdrawal thresholds were significantly lower than the 2 h post-treatment value (P<0.001). In rats treated with morphine plus Mrz 2/579, thresholds remained significantly higher between 10--72 h post-implantation than with morphine alone (P<0.05). In contrast, infusion of the same level of Mrz 2/579 once tolerance had developed did not reverse tolerance. These results indicate that fast NMDA channel blockers such as Mrz 2/579 may prove to be useful in enhancing analgesia to continuous morphine administration.

Evaluation of Soft Tissue Reaction to Corundum Ceramic Implants Infiltrated with Colloidal Silver.

PubMed

Wnukiewicz, Witold; Rutowski, Roman; Zboromirska-Wnukiewicz, Beata; Reichert, Paweł; Gosk, Jerzy

2016-01-01

Corundum ceramic is a biomaterial used as a bone graft substitute. Silver is a well known antiseptic substance with many practical, clinical applications. The aim of this study was to estimate soft tissue (in vivo) reaction to a new kind of ceramic implants. In our experiment, we examined the soft tissue reaction after implantation of corundum ceramic infiltrated with colloidal silver in the back muscles of 18 Wistar rats. The use of colloidal silver as a coating for the implant was designed to protect it against colonization by bacteria and the formation of bacterial biofilm. In our study, based on the experimental method, we performed implantation operations on 18 Wistar rats. We implanted 18 modified ceramic implants and, as a control group, 18 unmodified implants. As a follow up, we observed the animals operated upon, and did postoperative, autopsy and histopathological examinations 14, 30, 90 and 180 days after implantation. We didn't observe any pathological reactions and significant differences between the soft tissue reaction to the modified implants and the control group. Lack of pathological reaction to the modified implants in the living organism is the proof of their biocompatibility. This is, of course, the first step on the long path to introduce a new kind of biocompatible ceramic implant with antiseptic cottage. Our experiment has an only introductory character and we plan to perform other, more specific, tests of this new kind of implant.

Effect of topically applied minoxidil on the survival of rat dorsal skin flap.

PubMed

Gümüş, Nazım; Odemiş, Yusuf; Yılmaz, Sarper; Tuncer, Ersin

2012-12-01

Flap necrosis still is a challenging problem in reconstructive surgery that results in irreversible tissue loss. This study evaluated the effect of topically applied minoxidil on angiogenesis and survival of a caudally based dorsal rat skin flap. For this study, 24 male Wistar rats were randomly divided into three groups of eight each. A caudally based dorsal skin flap with the dimensions of 9 × 3 cm was raised. After elevation of the flaps, they were sutured back into their initial positions. In group 1 (control group), 1 ml of isotonic saline was applied topically to the flaps of all the animals for 14 days. In group 2, minoxidil solution was spread uniformly over the flap surface for 7 days after the flap elevation. In group 3, minoxidil solution was applied topically to the flap surface during a 14-day period. On day 7 after the flap elevation, the rats were killed. The average area of flap survival was determined for each rat. Subdermal vascular architecture and angiogenesis were evaluated under a light microscope after two full-thickness skin biopsy specimens had been obtained from the midline of the flaps. The lowest flap survival rate was observed in group 1, and no difference was observed between groups 1 and 2. Compared with groups 1 and 2, group 3 had a significantly increased percentage of flap survival (P < 0.05). Intense and moderate angiogenesis also was observed respectively at the proximal and distal areas of the flaps in group 3. The results of this experiment seem to show that the early effect of minoxidil is vasodilation and that prolonged use before flap elevation leads to angiogenesis, increasing flap viability. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model.

PubMed

Chen, Sung-Hsiung; Huang, Shun-Chen; Lui, Chun-Chung; Lin, Tzu-Ping; Chou, Fong-Fu; Ko, Jih-Yang

2012-09-01

Implantation of TheraCyte 4 × 10(6) live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model. Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N = 20); Group 2 rats were implanted with TheraCyte-encapsulated 4 × 10(6) live parathyroid cells into the subcutis of their necks (TheraCyte; N = 20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH). Based on manual palpation, the control group had a fusion rate of 33 % (6/18) and the TheraCyte group had a fusion rate of 72 % (13/18) (P = 0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P < 0.05); neither serum calcium nor phosphorus levels were significantly different between the two groups. This pilot animal study revealed that there were more fusions in rats that received TheraCyte-encapsulated 4 × 10(6) live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.

Tio2-dopamine complex implanted unilaterally in the caudate nucleus improves motor activity and behavior function of rats with induced hemiparkinsonism.

PubMed

Vergara-Aragón, Patricia; Domínguez-Marrufo, Leonardo Eduardo; Ibarra-Guerrero, Patricia; Hernandez-Ramírez, Heidi; Hernández-Téllez, Beatriz; López-Martínez, Irma Elena; Sánchez-Cervantes, Ivonne; Santiago-Jacinto, Patricia; García-Macedo, Jorge Alberto; Valverde-Aguilar, Guadalupe; Santiago, Julio

2011-01-01

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

Effects of larval tapeworm (Taenia taeniaeformis) infection on reproductive functions in male and female host rats.

PubMed

Lin, Y C; Rikihisa, Y; Kono, H; Gu, Y

1990-04-01

This report examined the effects of larval tapeworm infection on the reproductive functions in both male and female host rats. Female rats were matched by age, then randomly assigned to control and treatment groups (infected with larval tapeworms). Estrous cycles were determined by vaginal smear with 95% of the control group exhibiting 4-day normal cyclicity and only 55% of the treated group exhibiting normal cycles. Female fertility was then evaluated for the normally cycling rats based on the percentage of successful matings on the evening of proestrus, number of implantation sites on Day 8 of pregnancy, and number of pups born at term. The normally cycling rats exhibited 96% successful mating, 12.95 +/- 1.80 implantation sites, and 11.20 +/- 1.80 pups born. Five months after larval tapeworm infection, the fertility parameters were decreased to 79%, 9.10 +/- 1.20, and 7.50 +/- 1.50, respectively. The control females were then used in a study of male fertility after larval tapeworm infection employing the same parameters used to test female fertility. At the onset of the study, control groups exhibited 95% successful mating, 12.50 +/- 1.50 implantation sites, and 11.60 +/- 1.60 pups born at full term. After the 5-month infection period, the parameters were substantially reduced to 29%, 6.20 +/- 0.80 implantation sites, and 5.10 +/- 0.80 pups, respectively. Average testosterone concentrations in serum and testis from control male rats were 8.80 +/- 0.95 ng/ml and 3.88 +/- 0.25 ng/mg protein, respectively. After the 5-month infection period, these levels were reduced to 2.47 +/- 0.31 ng/ml and 1.28 +/- 0.12 ng/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

PubMed

Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

2010-11-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

PubMed Central

Matveyenko, Aleksey V.; Georgia, Senta; Bhushan, Anil

2010-01-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant. PMID:20587750

Evaluation of egg white ovomucin-based porous scaffold as an implantable biomaterial for tissue engineering.

PubMed

Carpena, Nathaniel T; Abueva, Celine D G; Padalhin, Andrew R; Lee, Byong-Taek

2017-10-01

Studies have shown the technological and functional properties of ovomucin (OVN) in the food-agricultural industry. But research has yet to explore its potential as an implantable biomaterial for tissue engineering and regenerative medicine. In this study we isolated OVN from egg white by isoelectric precipitation and fabricated scaffolds with tunable porosity by utilizing its foaming property. Gelatin a known biocompatible material was introduced to stabilize the foams, wherein different ratios of OVN and gelatin had a significant effect on the degree of porosity, pore size and stability of the formed hydrogels. The porous scaffolds were crosslinked with EDC resulting in stable scaffolds with prolonged degradation. Improved cell proliferation and adhesion of rat bone marrow-derived mesenchymal stem cells were observed for OVN containing scaffolds. Although, scaffolds with 75% OVN showed decrease in cell proliferation for L929 fibroblast type of cells. Further biocompatibility assessment as implant material was determined by subcutaneous implantation in rats of selected scaffold. H&E staining showed reasonable vascularization over time and little evidence of severe fibrosis at the implant site. Persistent polarization of classically activated macrophage was not observed, potentially reducing inflammatory response, and showed increased expression of alternatively activated macrophage cells that is favorable for tissue repair. Analysis of IgE levels in rat serum after implantation indicated minimal and resolvable allergic response to the OVN implants. The results demonstrate OVN as an acceptable implant scaffold that could provide new opportunities as an alternative natural biocompatible and functional biomaterial in various biomedical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2107-2117, 2017. © 2016 Wiley Periodicals, Inc.

[Electroacupuncture Combined with Clomiphene Promotes Pregnancy and Blastocyst Implantation Possibly by Up-regulating Expression of Insulin Receptor and Insulin Receptor Substrate 1 Proteins in Endometrium in Rats with PCOS].

PubMed

Lai, Mao-Hua; Ma, Hong-Xia; Song, Xing-Hua

2016-10-25

To observe the effect of electroacupuncture (EA) intervention combined with clomiphene critate (CC) on the blastocyst implantation and pregnancy rate and expression of insulin receptor (INSR) and insulin receptor substrate 1 (IRS 1) proteins in the endometrium in rats with polycystic ovary syndrome (PCOS), so as to reveal its mechanisms underlying improvement of PCOS. One hundred and twenty-five female SD rats were randomly divided into normal control, PCOS model, medication (CC), EA and EA+CC groups ( n =25 in each group, 15 for checking blastocyst implantation, and 10 for Western blot). The PCOS model was established by subcutaneous injection of Dehydroepiandrosterone (DHEA) and fed with high-fat diet. Rats of the normal control group were treated by subcutaneous injection of sesame oil and fed with the normal forage. EA stimulation was applied to "Zhongwan" (CV 12), "Guanyuan" (CV 4) and bilateral "Tianshu" (ST 25) for 30 min, 3 times a week, 5 weeks altogether. Rats of the CC and EA+CC groups were fed with CC (100 mg·kg -1 ·d -1 ) for 2 days after regular restriction (30 min, 3 times a week, 5 weeks altogether). The pregnancy was determined by vaginal smear tests and the number of blastocyst implantation determined by examination of the uterus after execution. The expression of INSR and IRS 1 proteins in the endometrium was detected by Western blot. The pregnancy rate and the number of blastocyst implantation were significantly lower in the model group than in the normal control group ( P <0.05), and remarkably increased after EA and EA+CC interventions ( P <0.05). The effects of EA+CC were obviously superior to those of simple EA and simple medication in raising the pregnancy rate and the number of blastocyst implantation ( P <0.05). No significant differences were found between the EA and CC groups in the pregnancy rate and the number of blastocyst implantation ( P >0.05). The relative expression levels of both INSR and IRS 1 proteins were markedly lower in the model group than in the normal control group ( P <0.05), and significantly higher in both EA and EA+CC groups than in the model group ( P <0.05). No significant differences were found between the model and the CC groups and between the EA and EA+CC groups in the expression levels of INSR and IRS 1 proteins ( P >0.05). EA intervention can improve pregnancy rate and the number of blastocyst implantation in PCOS rats, which may be related to its effects in up-regulating the expression of INSR and IRS 1 proteins in the endometrium.

Biodegradable seeds of holmium don't change neurological function after implant in brain of rats.

PubMed

Diniz, Mirla Fiuza; Ferreira, Diogo Milioli; de Lima, Wanderson Geraldo; Pedrosa, Maria Lucia; Silva, Marcelo Eustáquio; de Almeida Araujo, Stanley; Sampaio, Kinulpe Honorato; de Campos, Tarcisio Passos Ribeiro; Siqueira, Savio Lana

2017-01-01

To evaluate the surgical procedure and parenchymal abnormalities related to implantation of ceramic seeds with holmium-165 in rats' brain. An effective method of cancer treatment is brachytherapy in which radioactive seeds are implanted in the tumor, generating a high local dose of ionizing radiation that can eliminate tumor cells while protecting the surrounding healthy tissue. Biodegradable Ho 166 -ceramic-seeds have been addressed recently. The experiments in this study were approved by the Ethics Committee on Animal Use at the Federal University of Ouro Preto, protocol number 2012/034. Twenty-one adult Fischer rats were divided into Naive Group, Sham Group and Group for seed implants (ISH). Surgical procedures for implantation of biodegradable seeds were done and 30 days after the implant radiographic examination and biopsy of the brain were performed. Neurological assays were also accomplished to exclude any injury resulting from either surgery or implantation of the seeds. Radiographic examination confirmed the location of the seeds in the brain. Neurological assays showed animals with regular spontaneous activity. The histological analysis showed an increase of inflammatory cells in the brain of the ISH group. Electron microscopy evidenced cytoplasmic organelles to be unchanged. Biochemical analyzes indicate there was neither oxidative stress nor oxidative damage in the ISH brain. CAT activity showed no difference between the groups as well as lipid peroxidation measured by TBARS. The analysis of the data pointed out that the performed procedure is safe as no animal showed alterations of the neurological parameters and the seeds did not promote histological architectural changes in the brain tissue.

Endothelial Cell Implantation and Survival within Experimental Gliomas

NASA Astrophysics Data System (ADS)

Lal, Bachchu; Indurti, Ravi R.; Couraud, Pierre-Olivier; Goldstein, Gary W.; Laterra, John

1994-10-01

The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the β-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by β-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation.

Bioacceptable and calcification-resistant membranes and interfaces for implantable sensors and devices

NASA Astrophysics Data System (ADS)

Galeska, Izabela Ewa

The rational design and characterization of biocompatible, semipermeable and calcification resistant materials to serve as an outer membrane for implantable glucose biosensors, was the primary focus of this research. Multilayered films of polyanions (i.e. Nafion(TM), a perfluorinated ionomer, and Humic Acids (HAs), naturally occurring biopolymers), fabricated by layer-by-layer self-assembly with oppositely charged ferric ions were investigated as potential membranes. Spectroscopic ellipsometry and quartz crystal microbalance studies point towards a stepwise film growth, with growth rates of 47 and 24.3 nm per layer (for Nafion and HAs respectively) that can be altered depending on the pH and ionic strength of the polyanion solution. Nafion/Fe3+ assembled films exhibited an order of magnitude lower calcification as compared to dip-coated Nafion films and did not require annealing to impart insolubility. Similarly the HAs/Fe3+ films were also devoid of calcification, even after four-week immersion in DMEM cell culture media. Significantly, in vivo studies on the HAs/Fe3 films point to their biocompatibility as demonstrated by mild tissue reaction. These results, along with controllable glucose permeability, could prove vital in prolonging the lifetime of implantable biosensors. Additionally in effort to minimize tissue trauma upon implantation, novel poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composites were investigated for dexamethasone delivery. A release rate of 25 to 40% over one month, following a zero order profile, was achieved by preferential adsorption of surface active polyacids (poly(acrylic acid), Nafion and HAs) on the hydrogel dispersed microspheres. Environmental scanning electron microscopy investigation on the degradation mechanism of the microspheres pointed towards their slow homogeneous degradation in the PVA hydrogels that was significantly surface-accelerated in the presence of polyacids. The physico-mechanical properties (fluid uptake and Young's modulus) and release of unencapsulated dexamethasone (80 to 100%) from the hydrogels were related to their crystallinity. Significantly, with Young's modulus in the range of 0.1 to 4 MPa, comparable to human sub-dermal tissue, the hydrated gels provide soft and flexible tissue/sensor interface.

Design and preparation of polyurethane-collagen/heparin-conjugated polycaprolactone double-layer bionic small-diameter vascular graft and its preliminary animal tests.

PubMed

Lu, Guang; Cui, Shi-Jun; Geng, Xue; Ye, Lin; Chen, Bing; Feng, Zeng-Guo; Zhang, Jian; Li, Zhong-Zhi

2013-04-01

People recently realized that it is important for artificial vascular biodegradable graft to bionically mimic the functions of the native vessel. In order to overcome the high risk of thrombosis and keep the patency in the clinical small-diameter vascular graft (SDVG) transplantation, a double-layer bionic scaffold, which can offer anticoagulation and mechanical strength simultaneously, was designed and fabricated via electrospinning technique. Heparin-conjugated polycaprolactone (hPCL) and polyurethane (PU)-collagen type I composite was used as the inner and outer layers, respectively. The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility was demonstrated by the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide (MTT) test in vitro and subcutaneous implants in vivo respectively. The grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post-transplantation. After angiography, the patent grafts were explanted for histological analysis. The double-layer bionic SDVG meet the clinical mechanical demand. Its good biocompatibility was proven by cytotoxicity experiment (the cell's relative growth rates (RGR) of PU-collagen outer layer were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%, 100.0% and 98.0%, on days 1, 3, and 5, respectively) and the subdermal implants experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs were patent without any aneurismal dilatation or obvious anastomotic stenosis at the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at the 2nd week. Histological analysis and SEM showed that the inner layer was covered by new endothelial-like cells. The double-layer bionic SDVG is a promising candidate as a replacement of native small-diameter vascular graft.

Neuroprotective Dose Response in RCS Rats Implanted with Microphotodiode Arrays

PubMed Central

Pardue, Machelle T.; Kim, Moon K.; Walker, Tiffany A.; Faulkner, Amanda E.; Chow, Alan Y.; Ciavatta, Vincent T.

2012-01-01

Purpose Neuropreservation of retinal function and structure in RCS rats following implantation of a microphotodiode array (MPA) has been shown in previous studies(Pardue et al. 2005a; Pardue et al. 2005b). Since microphotodiodes produce electrical currents in proportion to the intensity of incident light, increased light exposure may result in greater neuroprotective effects. Our previous studies suggested that the frequency of light exposure to electroretinogram (ERG) flash stimuli might provide increased neuroprotection. Thus, in this study, we examined the dose response of subretinal electrical stimulation by exposing RCS rats implanted with MPAs to variable durations and combinations of two different lighting regimens: pulsing incandescent bulbs and xenon stimuli from an ERG Ganzfeld. While incandescent light regimens did not produce any significant differences in ERG function, we found significantly greater dark-adapted ERG b-wave amplitudes in RCS rats that received weekly versus biweekly ERGs over the course of 8 weeks of follow-up. These results suggest that subretinal electrical stimulation may be optimized to produce greater neuroprotective effects by dosing with periodic higher current. PMID:22183323

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line.

PubMed

Terawaki, Kiyoshi; Sawada, Yumi; Kashiwase, Yohei; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Suzuki, Masami; Miyano, Kanako; Sudo, Yuka; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

2014-02-15

Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

[Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

PubMed

Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

2016-03-01

To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

A comparative study of zirconium and titanium implants in rat: osseointegration and bone material quality.

PubMed

Hoerth, Rebecca M; Katunar, María R; Gomez Sanchez, Andrea; Orellano, Juan C; Ceré, Silvia M; Wagermaier, Wolfgang; Ballarre, Josefina

2014-02-01

Permanent metal implants are widely used in human medical treatments and orthopedics, for example as hip joint replacements. They are commonly made of titanium alloys and beyond the optimization of this established material, it is also essential to explore alternative implant materials in view of improved osseointegration. The aim of our study was to characterize the implant performance of zirconium in comparison to titanium implants. Zirconium implants have been characterized in a previous study concerning material properties and surface characteristics in vitro, such as oxide layer thickness and surface roughness. In the present study, we compare bone material quality around zirconium and titanium implants in terms of osseointegration and therefore characterized bone material properties in a rat model using a multi-method approach. We used light and electron microscopy, micro Raman spectroscopy, micro X-ray fluorescence and X-ray scattering techniques to investigate the osseointegration in terms of compositional and structural properties of the newly formed bone. Regarding the mineralization level, the mineral composition, and the alignment and order of the mineral particles, our results show that the maturity of the newly formed bone after 8 weeks of implantation is already very high. In conclusion, the bone material quality obtained for zirconium implants is at least as good as for titanium. It seems that the zirconium implants can be a good candidate for using as permanent metal prosthesis for orthopedic treatments.

The “curved lead pathway” method to enable a single lead to reach any two intracranial targets

NASA Astrophysics Data System (ADS)

Ding, Chen-Yu; Yu, Liang-Hong; Lin, Yuan-Xiang; Chen, Fan; Lin, Zhang-Ya; Kang, De-Zhi

2017-01-01

Deep brain stimulation is an effective way to treat movement disorders, and a powerful research tool for exploring brain functions. This report proposes a “curved lead pathway” method for lead implantation, such that a single lead can reach in sequence to any two intracranial targets. A new type of stereotaxic system for implanting a curved lead to the brain of human/primates was designed, the auxiliary device needed for this method to be used in rat/mouse was fabricated and verified in rat, and the Excel algorithm used for automatically calculating the necessary parameters was implemented. This “curved lead pathway” method of lead implantation may complement the current method, make lead implantation for multiple targets more convenient, and expand the experimental techniques of brain function research.

Short term sodium alendronate administration improves the peri-implant bone quality in osteoporotic animals

PubMed Central

de OLIVEIRA, Danila; HASSUMI, Jaqueline Suemi; GOMES-FERREIRA, Pedro Henrique da Silva; POLO, Tárik Ocon Braga; FERREIRA, Gabriel Ramalho; FAVERANI, Leonardo Perez; OKAMOTO, Roberta

2017-01-01

Abstract Sodium alendronate is a bisphosphonate drug that exerts antiresorptive action and is used to treat osteoporosis. Objective The aim of this study was to evaluate the bone repair process at the bone/implant interface of osteoporotic rats treated with sodium alendronate through the analysis of microtomography, real time polymerase chain reactions and immunohistochemistry (RUNX2 protein, bone sialoprotein (BSP), alkaline phosphatase, osteopontin and osteocalcin). Material and Methods A total of 42 rats were used and divided in to the following experimental groups: CTL: control group (rats submitted to fictitious surgery and fed with a balanced diet), OST: osteoporosis group (rats submitted to a bilateral ovariectomy and fed with a low calcium diet) and ALE: alendronate group (rats submitted to a bilateral ovariectomy, fed with a low calcium diet and treated with sodium alendronate). A surface treated implant was installed in both tibial metaphyses of each rat. Euthanasia of the animals was conducted at 14 (immunhostochemistry) and 42 days (immunohistochemistry, micro CT and PCR). Data were subjected to statistical analysis with a 5% significance level. Results Bone volume (BV) and total pore volume were higher for ALE group (P<0.05). Molecular data for RUNX2 and BSP proteins were significantly expressed in the ALE group (P<0.05), in comparison with the other groups. ALP expression was higher in the CTL group (P<0.05). The immunostaining for RUNX2 and osteopontin was positive in the osteoblastic lineage cells of neoformed bone for the CTL and ALE groups in both periods (14 and 42 days). Alkaline phosphatase presented a lower staining area in the OST group compared to the CTL in both periods and the ALE at 42 days. Conclusion There was a decrease of osteocalcin precipitation at 42 days for the ALE and OST groups. Therefore, treatment with short-term sodium alendronate improved bone repair around the implants installed in the tibia of osteoporotic rats. PMID:28198975

Short and long effects of Citrullus colocynthis L. on reproductive system and fertility in female Spague-Dawley rats.

PubMed

Qazan, Walid Sh; Almasad, Motasem M; Daradka, Haytham

2007-08-15

Aim of this study is to investigate the toxic effects of Citrullus colocynthis L. (400 mg/kg/body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and Citrullus colocynthis L. were intraperitoneally injected to experimental animals in dose of 400 mg/kg/body wight. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using students t and Chi-square tests. The effect of Citrullus colocynthis L. exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Citrullus colocynthis L. for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Citrullus colocynthis L. were observed. Exposure to Citrullus colocynthis L. for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed a decrease in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Citrullus colocynthis L. causes adverse effects on the reproductive system and fertility.

The effect of hyperglycaemia on osseointegration: a review of animal models of diabetes mellitus and titanium implant placement.

PubMed

King, Shalinie; Klineberg, Iven; Levinger, Itamar; Brennan-Speranza, Tara C

2016-12-01

Patients with type 2 diabetes mellitus have a higher risk of dental and/or orthopaedic implant failure. However, the mechanism behind this phenomenon is unclear, and animal studies may prove useful in shedding light on the processes involved. This review considers the available literature on rat models of diabetes and titanium implantation. The process of osseointegration whereby direct contact is achieved between bone and an implant surface depends on healthy bone metabolism. Collective evidence suggests that hyperglycaemia adversely affects bone turnover and the quality of the organic matrix resulting in an overall deterioration in the quality, resilience and structure of the bone tissue. This in turn results in compromised osseointegration in patients receiving dental and orthopaedic implants. The incidence of diabetes mellitus (DM), which is a chronic metabolic disorder resulting in hyperglycaemia, is rising. Of particular significance is the rising incidence of adult onset type 2 diabetes mellitus (T2DM) in an ageing population. Understanding the effects of hyperglycaemia on osseointegration will enable clinicians to manage health outcomes for patients receiving implants. Much of our understanding of how hyperglycaemia affects osseointegration comes from animal studies. In this review, we critically analyse the current animal studies. Our review has found that most studies used a type 1 diabetes mellitus (T1DM) rodent model and looked at a young male population of rodents. The pathophysiology of T1DM is however very different to that of T2DM and is not representative of T2DM, the incidence of which is rising in the ageing adult population. Genetically modified rats have been used to model T2DM, but none of these studies have included female rats and the metabolic changes in bone for some of these models used are not adequately characterized. Therefore, the review suggests that the study population needs to be broadened to include both T1DM and T2DM models, older rats as well as young rats, and importantly animals from both sexes to reflect more accurately clinical practice.

Cellular responses to various levels of sustained delivery of testosterone in the ventral prostate.

PubMed

Cavett, W; Tucci, M; Cason, Z; Lemos, L; England, B; Tsao, A; Benghuzzi, H

1997-01-01

The objective of this study was to evaluate the effect of various dosages of testosterone (T) delivered in a sustained manner by means of tricalcium phosphate-lysine (TCPL) delivery system on morphological changes of prostatic tissue using adult male rats as a model. In this experiment, adult male rats (250-300 g BW) were randomly divided into five equal groups (n = 8). Rats in group I, II, and III were castrated and implanted subcutaneously with TCPL loaded with three different dosages (10, 100 and 200 mg T, respectively) of T. Rats in group IV were castrated and implanted with sharm TCPL capsules, and rats in group V served as intact unimplanted controls. Surgical aseptic techniques were performed according to standard laboratory procedures. At the end of 4 and 12 weeks post implantation, four animals from each group were sacrificed and the prostate tissues were collected, weighted, and embedded for histo-pathological evaluations. Data collected from this study have shown that exogenous intake of T delivered in a sustained manner for twelve weeks induced several pathophysiological conditions in ventral prostatic tissue in comparison to the control and sham operated groups. This phenomenon was found to be directly proportional to the dose or the level of sustained delivery. The results demonstrated that the use of 10 mg filled TCPL implants decreased the total mass weight of ventral prostate. Light microscopic evaluation of this group (Group I) revealed a cellular adaptation through an atrophy in the epithelium component. Cytopathological observations such as low cuboidal and thin glands, pleomorphism, and occasional presence of connective tissue stroma were detected. In contrast, ventral prostate collected from animals implanted with TCPL filled with 200 mg T (Group III) showed a significant increase in weights of the wet prostatic tissues in comparison to all groups. Histopathological evaluations demonstrated the following. (i) prostatic hypertrophy alone, or in conjunction with hyperplasia of the epithelial cells, (ii) less connective tissue stroma in comparison to the control group, (iii) occasional involvement of mitotic figures, and (iv) increased angiogenesis. No significant change was observed in those animals implanted with TCPL capsules containing 100 mg T compared to the intact control animals.

A long-acting buprenorphine delivery system.

PubMed

Pontani, R B; Misra, A L

1983-03-01

A subcutaneously implantable buprenorphine delivery system utilizing cholesterol-glyceryltristearate matrix for prolonged release of drug is described. Implantable cylindrical pellets of buprenorphine (cholesterol 36 mg, glyceryltristearate 4 mg, buprenorphine hydrochloride 10 mg), diameter 3 mm, length 6 mm blocked the antinociceptive action (hot plate, 55 degrees C) of 10 mg kg-1 SC challenge dose of morphine in rats for 12 weeks or more (longer periods not evaluated). The cumulative percent release of buprenorphine from the test devices 2, 4, 6, 10 and 12 weeks after implantation was 27.4, 35.9, 37.6, 39.9 and 43.1, respectively. The release of buprenorphine from 10 mg pellets approximated first-order kinetics with half-lives of 0.85 and 50.24 weeks, for alpha and beta phases, respectively. The test devices possess the desirable characteristics of simplicity, biocompatibility, nontoxicity, ease of sterilization with ethylene oxide, small size for ease of insertion and removal, minimal encapsulation by surrounding tissue and an extended period of drug release unaffected by body metabolism. No side effects were seen in implanted rats which fed well and gained weight during entire treatment. Neither deterioration of implant nor any gross anatomic changes at implant site were apparent 12 weeks after pellet implantation.

Visual evoked potential in RCS rats with Okayama University-type retinal prosthesis (OUReP™) implantation.

PubMed

Alamusi; Matsuo, Toshihiko; Hosoya, Osamu; Uchida, Tetsuya

2017-06-01

Photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis or OUReP™, generates light-evoked surface electric potentials and stimulates neurons. The dye-coupled films or plain films were implanted subretinally in both eyes of 10 Royal College of Surgeons rats with hereditary retinal dystrophy at the age of 6 weeks. Visual evoked potentials in response to monocular flashing light stimuli were recorded from cranially-fixed electrodes, 4 weeks and 8 weeks after the implantation. After the recording, subretinal film implantation was confirmed histologically in 7 eyes with dye-coupled films and 7 eyes with plain films. The recordings from these 7 eyes in each group were used for statistical analysis. The amplitudes of visual evoked potentials in the consecutive time points from 125 to 250 ms after flash were significantly larger in the 7 eyes with dye-coupled film implantation, compared to the 7 eyes with plain film implantation at 8 weeks after the implantation (P < 0.05, repeated-measure ANOVA). The photoelectric dye-coupled polyethylene film, as retinal prosthesis, gave rise to visual evoked potential in response to flashing light.

Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks.

PubMed

Scarsi, Kimberly K; Darin, Kristin M; Nakalema, Shadia; Back, David J; Byakika-Kibwika, Pauline; Else, Laura J; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E; Merry, Concepta; Lamorde, Mohammed

2016-03-15

Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus-infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. NCT01789879. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks

PubMed Central

Scarsi, Kimberly K.; Darin, Kristin M.; Nakalema, Shadia; Back, David J.; Byakika-Kibwika, Pauline; Else, Laura J.; Dilly Penchala, Sujan; Buzibye, Allan; Cohn, Susan E.; Merry, Concepta; Lamorde, Mohammed

2016-01-01

Background. Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics. Methods. This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus–infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies. Results. Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups. Conclusions. Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy. Clinical Trials Registration. NCT01789879. PMID:26646680

Angiogenesis after sintered bone implantation in rat parietal bone.

PubMed

Ohtsubo, S; Matsuda, M; Takekawa, M

2003-01-01

We studied the effect of bone substitutes on revascularization and the restart of blood supply after sintered bone implantation in comparison with synthetic hydroxyapatite implantation and fresh autogenous bone transplantation (control) in rat parietal bones. Methods for the study included the microvascular corrosion cast method and immunohistochemical techniques were also used. The revascularization of the control group was the same as that for usual wound healing in the observations of the microvascular corrosion casts. The sintered bone implantation group was quite similar to that of the control group. In the synthetic hydroxyapatite group, immature newly-formed blood vessels existed even on the 21st day after implantation and the physiological process of angiogenesis was interrupted. Immunohistochemically, vascular endothelial growth factor (VEGF), which activates angiogenesis, appeared at the early stages of both the control group and the sintered bone implantation group. VEGF reduced parallel with the appearance of the transforming growth factor factor-beta-1 (TGF-beta-1), which obstructs angiogenesis, and the angiogenesis passed gradually into the mature stage. In the hydroxyapatite implantation group, TGF-beta-1 appeared at the early stage of the implants. The appearance of VEGF lagged and it existed around the pores of hydroxyapatite even on the 21st day of the implantation. Proliferation and wandering of endothelial cells continued without any maturing of the vessels. These findings suggest that the structure and the components of the implant material affect angiogenesis after implantation as well as new bone formation.

Implantation loss induced by ethanolamine in the rat is ameliorated by a choline-supplemented diet.

PubMed

Moore, Nigel P; Wahl, Markus; Schneider, Steffen

2018-06-01

Ethanolamine (EA) reduced implantation success in a two-generation reproduction toxicity study; the aim of this work was to explore the underlying basis for this response. When administered to pregnant rats during gestation days (GD) 1-3, 4-5, or 6-7, EA had no effect upon implantation success. In a second experiment, EA was administered either in the diet or by oral gavage from two weeks prior to mating through to GD 8. Parallel groups also received a diet supplemented with choline. In the absence of supplementary choline, EA induced early resorptions, statistically significant only when administered in the diet. A slight reduction in implantation success was ameliorated by supplementary choline. We conclude that implantation is affected by EA only when exposure starts before mating; that dietary administration is more effective than gavage dosing; and that interference with choline homeostasis may play a role in the aetiology of this lesion. Copyright © 2018 Elsevier Inc. All rights reserved.

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve.

PubMed

Sarabia-Estrada, Rachel; Bañuelos-Pineda, Jacinto; Osuna Carrasco, Laura P; Jiménez-Vallejo, Salvador; Jiménez-Estrada, Ismael; Rivas-Celis, Efrain; Dueñas-Jiménez, Judith M; Dueñas-Jiménez, Sergio H

2015-07-01

Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes. Some gastrocnemius efferent fibers were partially repaired 90 days after nerve resection. The better outcome in knee angle displacement may be partially attributable to the aberrant neuromuscular synaptic effects, since nerve conduction in the gastrocnemius muscle could be blocked in the progesterone-impregnated chitosan tubes. In addition, in the region of the gap produced by the nerve resection, the number of axons and amount of myelination were reduced in the sciatic nerve implanted with chitosan, progesterone-loaded chitosan, and silicone tubes. At 180 days after sciatic nerve sectioning, the knee kinematic function recovered to a level observed in control rats of a similar age. In rats with progesterone-loaded chitosan tubes, stimulation of the proximal and intratubular sciatic nerve segments produced an electromyographic response. The axon morphology of the proximal and intratubular segments of the sciatic nerve resembled that of the contralateral nontransected nerve. Progesterone-impregnated chitosan tubes produced aberrant innervation of the gastrocnemius muscle, which allowed partial recovery of gait locomotion and could be adequate for reinnervating synergistic denervated muscles while a parent innervation is reestablished. Hindlimb kinematic parameters differed between younger (those at 90 days) and older (those at 180 days) rats.

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats.

PubMed

Hu, Min; Zhang, Yuehui; Feng, Jiaxing; Xu, Xue; Zhang, Jiao; Zhao, Wei; Guo, Xiaozhu; Li, Juan; Vestin, Edvin; Cui, Peng; Li, Xin; Wu, Xiao-Ke; Brännström, Mats; Shao, Linus R; Billig, Håkan

2018-05-01

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2 , two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions. © 2018 Society for Endocrinology.

Effect of avocado/soybean unsaponifiables on osseointegration: a proof-of-principle preclinical in vivo study.

PubMed

de Oliveira, Guilherme José Pimentel Lopes; de Paula, Luiz Guilherme Freitas; Spin-Neto, Rubens; Stavropoulos, Andreas; Spolidório, Luis Carlos; Marcantonio, Elcio; Marcantonio, Rosemary Adriana Chiérici

2014-01-01

To evaluate the influence of administration of avocado/soybean unsaponifiables (ASU) on implant osseointegration in rat tibiae. Thirty rats were randomly assigned into one of three equal-sized groups: (1) ASU1: administration of ASU starting 7 days prior to implant placement; (2) ASU2: administration of ASU starting on the day of implant placement, and (3) CTL: administration of saline solution. In all animals, one titanium implant was placed in each tibia. All animals received ASU or saline solution by gavage daily until sacrifice 60 days postoperatively. Implant osseointegration and bone maturation were assessed by biomechanical and radiographic bone density analysis; descriptive histology; immunohistochemistry for bone morphogenetic protein 2 (BMP-2), transforming growth factor beta 1 (TGF-β1), and osteocalcin; and histomorphometric evaluation of bone-to-implant contact (BIC) and mineralized bone area fraction within the threads of the implant. ASU1 and ASU2 showed three times higher expression of BMP-2 and nine times higher expression of TGF-β1 compared with CTL (P < .05). Histomorphometric analysis, however, showed that both ASU1 and ASU2 groups presented significantly higher BIC values only in the cortical bone compartment when compared to CTL (P < .05). ASU consumption seems to exert only a subtle effect on implant osseointegration.

Immunological Response to Biodegradable Magnesium Implants

NASA Astrophysics Data System (ADS)

Pichler, Karin; Fischerauer, Stefan; Ferlic, Peter; Martinelli, Elisabeth; Brezinsek, Hans-Peter; Uggowitzer, Peter J.; Löffler, Jörg F.; Weinberg, Annelie-Martina

2014-04-01

The use of biodegradable magnesium implants in pediatric trauma surgery would render surgical interventions for implant removal after tissue healing unnecessary, thereby preventing stress to the children and reducing therapy costs. In this study, we report on the immunological response to biodegradable magnesium implants—as an important aspect in evaluating biocompatibility—tested in a growing rat model. The focus of this study was to investigate the response of the innate immune system to either fast or slow degrading magnesium pins, which were implanted into the femoral bones of 5-week-old rats. The main alloying element of the fast-degrading alloy (ZX50) was Zn, while it was Y in the slow-degrading implant (WZ21). Our results demonstrate that degrading magnesium implants beneficially influence the immune system, especially in the first postoperative weeks but also during tissue healing and early bone remodeling. However, rodents with WZ21 pins showed a slightly decreased phagocytic ability during bone remodeling when the degradation rate reached its maximum. This may be due to the high release rate of the rare earth-element yttrium, which is potentially toxic. From our results we conclude that magnesium implants have a beneficial effect on the innate immune system but that there are some concerns regarding the use of yttrium-alloyed magnesium implants, especially in pediatric patients.

Biocompatibility of a polyether urethane, polypropylene oxide, and a polyether polyester copolymer. A qualitative and quantitative study of three alloplastic tympanic membrane materials in the rat middle ear.

PubMed

Bakker, D; van Blitterswijk, C A; Hesseling, S C; Koerten, H K; Kuijpers, W; Grote, J J

1990-04-01

The biocompatibility of porous implants made of Estane 5714 F1 polyether urethane, polypropylene oxide, and a poly(ethylene oxide hydantoin) and poly(tetramethylene terephthalate) segmented polyether polyester copolymer (HPOE/PBT copolymer), which were selected as candidates for an alloplastic tympanic membrane, was assessed after implantation in rat middle ears for periods of up to 1 year. Implantation of the materials led to tissue reactions initially associated with the wound-healing process, whereas after 1 month not only the presence of macrophages and foreign-body giant cells surrounding the implant materials but also implant degradation were characteristic for a foreign-body reaction. Macrophages and foreign-body giant cells dominated the picture of the tissue surrounding polypropylene oxide. The altered morphology of these cells, the persistent infiltration of the implantation sites by exudate cells, and the premature death of five rats in the 1-year group suggest that polypropylene oxide degradation was accompanied by the release of toxic substances. Estane and copolymer degradation did not induce tissue responses reflecting implant toxicity, and tympanic membranes given these alloplasts showed a normal healing pattern. Inclusions in the cytoplasm of macrophages associated with degradation and phagocytosis of all of the polymers under study were found to contain iron, silicon, titanium, and aluminum. Growth of fibrous tissue and bone, the latter into Estane and HPOE/PBT copolymer implants, indicated appropriate implant fixation by tissue, although macrophages and foreign-body giant cells were present as well. Especially the fixation of copolymer by ingrowth of bone seems promising in terms of the amount of bone in the pores and the electron-dense bone/copolymer interface. The latter is indicative for bonding osteogenesis. The HPOE/PBT copolymer is a better candidate for alloplastic tympanic membrane than Estane, and the use of polypropylene oxide cannot be recommended.

Mechanisms of electrode induced injury. Part 2: Clinical experience.

PubMed

Patterson, Terry; Stecker, Mark M; Netherton, Brett L

2007-06-01

In the previous paper in this series, basic mechanisms of electrode related injuries were discussed. In this paper, the discussion begins with some of the clinical aspects of burns. This is followed by a summary of the clinical literature on injuries produced by surface and subdermal electrodes. This clinical literature demonstrates that most electrode burns are related to the presence of high frequency electric fields (RF) created either by an electrosurgical unit or a magnetic resonance imaging (MRI) scanner. A smaller number of lesions are produced by low current, long duration direct current (DC) stimulation and during high current stimulation such as defibrillation. A discussion of the clinical complications from indwelling intracranial electrodes centers on electrodes placed for deep brain stimulation (DBS) that are currently used therapeutically in a wide array of neurologic disorders. The probability of considering a post-implant MRI scan is high and the safety of such scans is the focus of discussion. A very small number of adverse incidents have indicated a downward revision in the specific absorption rate recommendations for MRI examination with those patients who present with indwelling DBS leads and internal pulse generators. Continued vigilance when any type of electrode is used is important.

Confocal laser scanning microscopy in study of bone calcification

NASA Astrophysics Data System (ADS)

Nishikawa, Tetsunari; Kokubu, Mayu; Kato, Hirohito; Imai, Koichi; Tanaka, Akio

2012-12-01

Bone regeneration in mandible and maxillae after extraction of teeth or tumor resection and the use of rough surface implants in bone induction must be investigated to elucidate the mechanism of calcification. The calcified tissues are subjected to chemical decalcification or physical grinding to observe their microscopic features with light microscopy and transmission electron microscopy where the microscopic tissue morphology is significantly altered. We investigated the usefulness of confocal laser scanning microscopy (CLSM) for this purpose. After staggering the time of administration of calcein and alizarin red to experimental rats and dogs, rat alveolar bone and dog femur grafted with coral as scaffold or dental implants were observed with CLSM. In rat alveolar bone, the calcification of newly-formed bone and net-like canaliculi was observed at the mesial bone from the roots progressed at the rate of 15 μm/day. In dog femur grafted with coral, newly-formed bones along the space of coral were observed in an orderly manner. In dog femur with dental implants, after 8 weeks, newly-formed bone proceeded along the rough surface of the implants. CLSM produced high-magnification images of newly-formed bone and thin sections were not needed.

Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

PubMed Central

Luu, H M; Hutter, J C

2001-01-01

We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasiloxane (D(4)) after intravenous (IV), inhalation, or implantation exposures. The model used (14)C-D(4) IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D(4) after inhalation to experimental results in both rats and humans. We then used the model to simulate D(4) kinetics after single and/or repeated D(4) exposures in rats and humans. The model predicted bioaccumulation of D(4) in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log P(oct/water) = 5.1), D(4) persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D(4) in fatty tissues should play an important role in the risk assessment of D(4) especially in women exposed daily to multiple personal care products and silicone breast implants. PMID:11712992

Multilayer cell-seeded polymer nanofiber constructs for soft-tissue reconstruction.

PubMed

Barker, Daniel A; Bowers, Daniel T; Hughley, Brian; Chance, Elizabeth W; Klembczyk, Kevin J; Brayman, Kenneth L; Park, Stephen S; Botchwey, Edward A

2013-09-01

Cell seeding throughout the thickness of a nanofiber construct allows for patient-specific implant alternatives with long-lasting effects, earlier integration, and reduced inflammation when compared with traditional implants. Cell seeding may improve implant integration with host tissue; however, the effect of cell seeding on thick nanofiber constructs has not been studied. To use a novel cell-preseeded nanofiber tissue engineering technique to create a 3-dimensional biocompatible implant alternative to decellularized extracellular matrix. Animal study with mammalian cell culture to study tissue engineered scaffolds. Academic research laboratory. Thirty-six Sprague-Dawley rats. The rats each received 4 implant types. The grafts included rat primary (enhanced green fluorescent protein-positive [eGFP+]) fibroblast-seeded polycaprolactone (PCL)/collagen nanofiber scaffold, PCL/collagen cell-free nanofiber scaffold, acellular human cadaveric dermis (AlloDerm), and acellular porcine dermis (ENDURAGen). Rats were monitored postoperatively and received enrofloxacin in the drinking water for 4 days prophylactically and buprenorphine (0.2-0.5 mg/kg administered subcutaneously twice a day postoperatively for pain for 48 hours). The viability of NIH/3T3 fibroblasts cultured on PCL electrospun nanofibers was evaluated using fluorescence microscopy. Soft-tissue remodeling was examined histologically and with novel ex vivo volume determinations of implants using micro-computed tomography of cell-seeded implants relative to nanofibers without cells and commonly used dermal grafts of porcine and human origin (ENDURAGen and AlloDerm, respectively). The fate and distribution of eGFP+ seeded donor fibroblasts were assessed using immunohistochemistry. Fibroblasts migrated across nanofiber layers within 12 hours and remained viable on a single layer for up to 14 days. Scanning electron microscopy confirmed a nanoscale structure with a mean (SD) diameter of 158 (72) nm. Low extrusion rates demonstrated the excellent biocompatibility in vivo. Histological examination of the scaffolds demonstrated minimal inflammation. Cell seeding encouraged rapid vascularization of the nanofiber implants. Cells of donor origin (eGFP+) declined with the duration of implantation. Implant volume was not significantly affected for up to 8 weeks by the preseeding of cells (P > .05). Polymer nanofiber-based scaffolds mimic natural extracellular matrix. Preseeding the nanofiber construct with cells improved vascularization without notable effects on volume. An effect of cell preseeding on scaffold vascularization was evident beyond the presence of preseeded cells. This 3-dimensional, multilayer method of cell seeding throughout a 1-mm-thick construct is simple and feasible for clinical application. Further development of this technique may affect the clinical practice of facial plastic and reconstructive surgeons.

Towards continuous glucose monitoring: in vivo evaluation of a miniaturized glucose sensor implanted for several days in rat subcutaneous tissue.

PubMed

Moatti-Sirat, D; Capron, F; Poitout, V; Reach, G; Bindra, D S; Zhang, Y; Wilson, G S; Thévenot, D R

1992-03-01

A miniaturized amperometric, enzymatic, glucose sensor (outer diameter 0.45 mm) was evaluated after implantation in the subcutaneous tissue of normal rats. A simple experimental procedure was designed for the long-term assessment of the sensor's function which was performed by recording the current during an intraperitoneal glucose load. The sensor was calibrated by accounting for the increase in the current during the concomitant increase in plasma glucose concentration, determined in blood sampled at the tail vein. This made it possible to estimate the glucose concentration in subcutaneous tissue. During the glucose load, the change in subcutaneous glucose concentration followed that in blood with a lag time consistently shorter than 5 min. The estimations of subcutaneous glucose concentration during these tests were compared to the concomitant plasma glucose concentrations by using a grid analysis. Three days after implantation (n = 6 experiments), 79 estimations were considered accurate, except for five which were in the acceptable zone. Ten days after implantation (n = 5 experiments), 101 estimations were accurate, except for one value, which was still acceptable. The sensitivity was around 0.5 nA.mmol-1.l-1 on day 3 and day 10. A longitudinal study on seven sensors tested on different days demonstrated a relative stability of the sensor's sensitivity. Finally, histological examination of the zone around the implantation site revealed a fibrotic reaction containing neocapillaries, which could explain the fast response of the sensor to glucose observed in vivo, even on day 10. We conclude that this miniaturized glucose sensor, whose size makes it easily implanted, works for at least ten days after implantation into rat subcutaneous tissue.

Effects of MgO and SiO2 on Plasma-Sprayed Hydroxyapatite Coating: An in Vivo Study in Rat Distal Femoral Defects.

PubMed

Ke, Dongxu; Robertson, Samuel F; Dernell, William S; Bandyopadhyay, Amit; Bose, Susmita

2017-08-09

Plasma-sprayed hydroxyapatite (HA)-coated titanium implants have been widely used in orthopedic applications due to their inheritance of an excellent mechanical property from titanium and great osteoconductivity from HA. However, the lack of osteoinductivity limits their further applications. In this study, 1 wt % MgO and 0.5 wt % SiO 2 were mixed with HA for making plasma-sprayed coatings on titanium implants. Plasma-sprayed HA- and MgO/SiO 2 -HA-coated titanium implants showed adhesive bond strengths of 25.73 ± 1.92 and 23.44 ± 2.89 MPa, respectively. The presence of MgO and SiO 2 significantly increased the osteogenesis, osseointegration, and bone mineralization of HA-coated titanium implants by the evaluation of their histomorphology after 6, 10, and 14 weeks of implantation in rat distal femoral defects. Implant pushout tests also showed a shear modulus of 149.83 ± 3.69 MPa for MgO/SiO 2 -HA-coated implants after 14 weeks of implantation, compared to 52.68 ± 10.41 MPa for uncoated implants and 83.92 ± 3.68 MPa for pure HA-coated implants; These are differences in the shear modulus of 96% and 56.4%, respectively. This study assesses for the first time the quality of the bone-implant interface of induction plasma-sprayed MgO and SiO 2 binary-doped HA coatings on load-bearing implants compared to bare titanium and pure HA coatings in a quantitative manner. Relating the osseointegration and interface shear modulus to the quality of implant fixation is critical to the advancement and implementation of HA-coated orthopedic implants.

A new Fe-Mn-Si alloplastic biomaterial as bone grafting material: In vivo study

NASA Astrophysics Data System (ADS)

Fântânariu, Mircea; Trincă, Lucia Carmen; Solcan, Carmen; Trofin, Alina; Strungaru, Ştefan; Şindilar, Eusebiu Viorel; Plăvan, Gabriel; Stanciu, Sergiu

2015-10-01

Designing substrates having suitable mechanical properties and targeted degradation behavior is the key's development of bio-materials for medical application. In orthopedics, graft material may be used to fill bony defects or to promote bone formation in osseous defects created by trauma or surgical intervention. Incorporation of Si may increase the bioactivity of implant locally, both by enhancing interactions at the graft-host interface and by having a potential endocrine like effect on osteoblasts. A Fe-Mn-Si alloy was obtained as alloplastic graft materials for bone implants that need long recovery time period. The surface morphology of the resulted specimens was investigated using scanning electrons microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffractions (X'Pert equipment) or X-ray dispersive energy analyze (Bruker EDS equipment). This study objective was to evaluate in vivo the mechanisms of degradation and the effects of its implantation over the main metabolic organs. Biochemical, histological, plain X radiography and computed tomography investigations showed good compatibility of the subcutaneous implants in the rat organism. The implantation of the Fe-Mn-Si alloy, in critical size bone (tibiae) defect rat model, did not induced adverse biological reactions and provided temporary mechanical support to the affected bone area. The biodegradation products were hydroxides layers which adhered to the substrate surface. Fe-Mn-Si alloy assured the mechanical integrity in rat tibiae defects during bone regeneration.

[Implantation of flakes of castor oil resin in rat dental alveolus].

PubMed

Calixto, R F; Teófilo, J M; Brentegani, L G; Carvalho, T L

2001-01-01

The purposes of the present study were: 1) to investigate the biocompatibility of a natural resin (made of fatty acids extracted from Ricinus communis) implanted in the dental alveolus of rats and 2) to verify any possible interference of that material in the osseous healing following tooth extraction. The resin (AUG-EX, Poliquil Araraquara Polímeros Químicos LTDA, Araraquara--SP) was placed inside de alveoli immediately after extraction of the upper right incisors. The animals were sacrificed 1, 2, 3 and 6 weeks after extraction or extraction + implantation. The hemi-maxillae were decalcified and processed for paraffin embedding. Longitudinal 6-micrometer-thick semi-serial sections stained with hematoxylin and eosin were obtained. Histologic examination showed particles of irregular shape and variable size (700-1200 microns) localized in the medium/cervical alveolar thirds, with a scanty but persistent foreign body reaction. From the second week on, as the relative volume of bone trabeculae increased, it was seen in close contact with the surface of the implanted material in some regions. Histometric analysis (differential point counting method), used to quantify the healing process in the apical third, showed a small but significant decrease (13%-20%) in new bone formation in the implanted rats. In conclusion, the results show that, in spite of its biocompatible nature, the studied resin hinders the post-extration healing process.

Osteogenic efficacy of strontium hydroxyapatite micro-granules in osteoporotic rat model.

PubMed

Chandran, Sunitha; Babu S, Suresh; Vs, Hari Krishnan; Varma, H K; John, Annie

2016-10-01

Excessive demineralization in osteoporotic bones impairs its self-regeneration potential following a defect/fracture and is of great concern among the aged population. In this context, implants with inherent osteogenic ability loaded with therapeutic ions like Strontium (Sr 2+ ) may bring forth promising outcomes. Micro-granular Strontium incorporated Hydroxyapatite scaffolds have been synthesized and in vivo osteogenic efficacy was evaluated in a long-term osteoporosis-induced aged (LOA) rat model. Micro-granules with improved surface area are anticipated to resorb faster and together with the inherent bioactive properties of Hydroxyapatite with the leaching of Strontium ions from the scaffold, osteoporotic bone healing may be promoted. Long-term osteoporosis-induced aged rat model was chosen to extrapolate the results to clinical osteoporotic condition in the aged. Micro-granular 10% Strontium incorporated Hydroxyapatite synthesized by wet precipitation method exhibited increased in vitro dissolution rate and inductively coupled plasma studies confirmed Strontium ion release of 0.01 mM, proving its therapeutic potential for osteoporotic applications. Wistar rats were induced to long-term osteoporosis-induced aged model by ovariectomy along with a prolonged induction period of 10 months. Thereafter, osteogenic efficacy of Strontium incorporated Hydroxyapatite micro-granules was evaluated in femoral bone defects in the long-term osteoporosis-induced aged model. Post eight weeks of implantation in vivo regeneration efficacy ratio was highest in the Strontium incorporated Hydroxyapatite implanted group (0.92 ± 0.04) compared to sham and Hydroxyapatite implanted group. Micro CT evaluation further substantiated the improved osteointegration of Strontium incorporated Hydroxyapatite implants from the density histograms. Thus, the therapeutical potential of micro-granular Strontium incorporated Hydroxyapatite scaffolds becomes relevant, especially as bone void fillers in osteoporotic cases of tumor resection or trauma. © The Author(s) 2016.

Implantable batteryless device for on-demand and pulsatile insulin administration

NASA Astrophysics Data System (ADS)

Lee, Seung Ho; Lee, Young Bin; Kim, Byung Hwi; Lee, Cheol; Cho, Young Min; Kim, Se-Na; Park, Chun Gwon; Cho, Yong-Chan; Choy, Young Bin

2017-04-01

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Preliminary Study on Intrasplenic Implantation of Artificial Cell Bioencapsulated Stem Cells to Increase the Survival of 90% Hepatectomized Rats

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

We implanted artificial cell bioencapsulated bone marrow mesenchymal stem cells into the spleens of 90% hepatectomized (PH) rats. The resulting 14 days survival rate was 91%. This is compared to a survival rate of 21% in 90% hepatectomized rats and 25% for those receiving free MSCs transplanted the same way. Unlike free MSCs, the bioencapsulated MSCs are retained in the spleens and their hepatotrophic factors can continue to drain directly into the liver without dilution resulting in improved hepatic regeneration. In addition, with time the transdifferentiation of MSCs into hepatocyte-like cells in the spleen renders the spleen as a ectopic liver support. PMID:19132579

Real-time Seizure Detection System Using Multiple Single-Neuron Recordings

DTIC Science & Technology

2001-10-25

electrodes were implanted bilaterally into the temporal lobe of each rat. The rats were anesthetized with nebutal (50mg/kg). Small craniotomies were...1997. [9] Fanselow, E.E., Reid, A.P., Nicolelis, M.A.L., Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered

ATRAZINE EFFECTS ON EARLY PREGNANCY AND IMPLANATION IN THE RAT

EPA Science Inventory

Atrazine Effects on Early Pregnancy and Implantation in the Rat.
A.M. Cummings, B.E. Rhodes*, and R.L. Cooper*.
Reproductive Toxicology Division, NHEERL, USEPA, Research Triangle Park, NC
Atrazine (ATR), an herbicide, can induce mammary tumors in rats. ATR can also sup...

Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts

PubMed Central

Song, Heesang; Hwang, Hye Jin; Chang, Woochul; Song, Byeong-Wook; Cha, Min-Ji; Lim, Soyeon; Choi, Eun Ju; Ham, Onju; Lee, Chang Youn; Park, Jun-Hee; Lee, Se-Yeon; Choi, Eunmi; Lee, Chungkeun; Lee, Myoungho; Lee, Moon-Hyoung; Kim, Sung-Hou; Jang, Yangsoo; Hwang, Ki-Chul

2011-01-01

Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an optimal cell type has not yet emerged in terms of electromechanical integration in infarcted myocardium. We found that poor to moderate survival benefits of MSC-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted MSCs in the infarcted myocardium. Here, we report the development of cardiogenic cells from rat MSCs activated by phorbol myristate acetate, a PKC activator, that exhibited high expressions of cardiac-specific markers and Ca2+ homeostasis-related proteins and showed adrenergic receptor signaling by norepinephrine. Histological analysis showed high connexin 43 coupling, few inflammatory cells, and low fibrotic markers in myocardium implanted with these phorbol myristate acetate-activated MSCs. Infarct hearts implanted with these cells exhibited restoration of conduction velocity through decreased tissue heterogeneity and improved myocardial contractility. These findings have major implications for the development of better cell types for electromechanical integration of cell-based treatment for infarcted myocardium. PMID:21173226

Pharmacokinetics and biodegradation of chitosan in rats

NASA Astrophysics Data System (ADS)

Li, Hui; Jiang, Zhiwen; Han, Baoqin; Niu, Shuyi; Dong, Wen; Liu, Wanshun

2015-10-01

Chitosan, an excellent biomedical material, has received a widespread in vivo application. In contrast, its metabolism and distribution once being implanted were less documented. In this study, the pharmacokinetics and biodegradation of fluorescein isothiocyanate (FITC) labeled and muscle implantation administrated chitosan in rats were investigated with fluorescence spectrophotometry, histological assay and gel chromatography. After implantation, chitosan was degraded gradually during its distribution to diverse organs. Among the tested organs, liver and kidney were found to be the first two highest in chitosan content, which was followed by heart, brain and spleen. Urinary excretion was believed to be the major pathway of chitosan elimination, yet 80% of chitosan administered to rats was not trackable in their urine. This indicated that the majority of chitosan was degraded in tissues. In average, the molecular weight of the degradation products of chitosan in diverse organs and urine was found to be <65 kDa. This further confirmed the in vivo degradation of chitosan. Our findings provided new evidences for the intensive and safe application of chitosan as a biomedical material.

[Abdominal wall reconstruction with collagen membrane in an animal model of abdominal hernia. A preliminary report].

PubMed

Łukasiewicz, Aleksander; Drewa, Tomasz; Skopińska-Wiśniewska, Joanna; Molski, Stanisław

2008-01-01

Abdominal hernia repair is one of the most common surgical procedures. Current data indicate that the best treatment results are achieved with use of synthetic material to reinforce weakened abdominal wall. Prosthetic materials utilized for hernia repair induce adhesions with underlying viscera. They should be therefore separated from them by a layer of peritoneum otherwise adhesions may cause to serious complications such as bowel-skin fistulas. The aim of our work was to determine if implantation of our collagen membrane into abdominal wall defect induce adhesions in rat model of ventral hernia. The collagen film was obtained by acetic acid extraction of rat tail tendons and than casting the soluble fraction onto polyethylene shits. Abdominal wall defect was created in 10 Wistar male rats. Collagen membranes were implanted into the defect using interrupted polypropylene stitches. After 3 months of observation all animals were sacrificed. No adhesions between path structure and bowel developed. In one often rats (10%) adhesion between fixating stitch and omentum was observed. Complete mesothelium lining and vascular ingrowth were microscopically observed within implanted structure. Promising result requires further confirmation in a larger series of animals.

The effects of thyroxine on metabolism and water balance in a desert-dwelling rodent, Merriam's kangaroo rat (Dipodomys merriami).

PubMed

Banta, Marilyn R; Holcombe, Dale W

2002-01-01

Desert-dwelling mammals such as Merriam's kangaroo rat (Dipodomys merriani) need to conserve both energy and water to survive desert conditions characterized by aridity and low productivity. The thyroid hormone thyroxine increases both basal metabolic rate and urinary water loss in mammals. Increases in basal metabolism and urinary water loss are likely to be detrimental to D. merriami, therefore the regulation of this hormone may be important. To examine the effects of thyroxine in this species, we implanted adult kangaroo rats with pellets designed to release specific doses of thyroxine at a constant rate for 90 days or a placebo pellet. We measured plasma thyroxine concentration, basal metabolic rate, food consumption, urine concentration and water loss in all implanted animals. Thyroxine implants significantly increased both plasma thyroxine and basal metabolic rate in a relatively dose-dependent manner. In response to thyroxine. kangaroo rats increased food consumption only slightly, but this small increase was sufficient to compensate for their elevated metabolic rates. Neither urine concentration nor water loss varied among treatment groups. Thyroxine increased energy expenditure but not water loss in this species.

Biofunctionalization of a titanium surface with a nano-sawtooth structure regulates the behavior of rat bone marrow mesenchymal stem cells

PubMed Central

Zhang, Wenjie; Li, Zihui; Liu, Yan; Ye, Dongxia; Li, Jinhua; Xu, Lianyi; Wei, Bin; Zhang, Xiuli; Liu, Xuanyong; Jiang, Xinquan

2012-01-01

Background: The topography of an implant surface can serve as a powerful signaling cue for attached cells and can enhance the quality of osseointegration. A series of improved implant surfaces functionalized with nanoscale structures have been fabricated using various methods. Methods: In this study, using an H2O2 process, we fabricated two size-controllable sawtooth-like nanostructures with different dimensions on a titanium surface. The effects of the two nano-sawtooth structures on rat bone marrow mesenchymal stem cells (BMMSCs) were evaluated without the addition of osteoinductive chemical factors. Results: These new surface modifications did not adversely affect cell viability, and rat BMMSCs demonstrated a greater increase in proliferation ability on the surfaces of the nano-sawtooth structures than on a control plate. Furthermore, upregulated expression of osteogenic-related genes and proteins indicated that the nano-sawtooth structures promote osteoblastic differentiation of rat BMMSCs. Importantly, the large nano-sawtooth structure resulted in the greatest cell responses, including increased adhesion, proliferation, and differentiation. Conclusion: The enhanced adhesion, proliferation, and osteogenic differentiation abilities of rat BMMSCs on the nano-sawtooth structures suggest the potential to induce improvements in bone-titanium integration in vivo. Our study reveals the key role played by the nano-sawtooth structures on a titanium surface for the fate of rat BMMSCs and provides insights into the study of stem cell-nanostructure relationships and the related design of improved biomedical implant surfaces. PMID:22927760

Suprapubic Bladder Catheterization of Male Spinal-Cord–Injured Sprague–Dawley Rats

PubMed Central

Robinson, Mary A; Herron, Alan J; Goodwin, Bradford S; Grill, Raymond J

2012-01-01

The rat spinal-cord–injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine. PMID:22330872

Pulp Cell Tracking by Radionuclide Imaging for Dental Tissue Engineering

PubMed Central

Souron, Jean-Baptiste; Petiet, Anne; Decup, Franck; Tran, Xuan Vinh; Lesieur, Julie; Poliard, Anne; Le Guludec, Dominique; Letourneur, Didier; Chaussain, Catherine; Rouzet, Francois

2014-01-01

Pulp engineering with dental mesenchymal stem cells is a promising therapy for injured teeth. An important point is to determine the fate of implanted cells in the pulp over time and particularly during the early phase following implantation. Indeed, the potential engraftment of the implanted cells in other organs has to be assessed, in particular, to evaluate the risk of inducing ectopic mineralization. In this study, our aim was to follow by nuclear imaging the radiolabeled pulp cells after implantation in the rat emptied pulp chamber. For that purpose, indium-111-oxine (111In-oxine)-labeled rat pulp cells were added to polymerizing type I collagen hydrogel to obtain a pulp equivalent. This scaffold was implanted in the emptied pulp chamber space in the upper first rat molar. Labeled cells were then tracked during 3 weeks by helical single-photon emission computed tomography (SPECT)/computed tomography performed on a dual modality dedicated small animal camera. Negative controls were performed using lysed radiolabeled cells obtained in a hypotonic solution. In vitro data indicated that 111In-oxine labeling did not affect cell viability and proliferation. In vivo experiments allowed a noninvasive longitudinal follow-up of implanted living cells for at least 3 weeks and indicated that SPECT signal intensity was related to implanted cell integrity. Notably, there was no detectable systemic release of implanted cells from the tooth. In addition, histological analysis of the samples showed mitotically active fibroblastic cells as well as neoangiogenesis and nervous fibers in pulp equivalents seeded with entire cells, whereas pulp equivalents prepared from lysed cells were devoid of cell colonization. In conclusion, our study demonstrates that efficient labeling of pulp cells can be achieved and, for the first time, that these cells can be followed up after implantation in the tooth by nuclear imaging. Furthermore, it appears that grafted cells retained the label and are viable to follow the repair process. This technique is expected to be of major interest for monitoring implanted cells in innovative therapies for injured teeth. PMID:23789732

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats

PubMed Central

Zhang, Yifeng; Xu, Jiankun; Ruan, Ye Chun; Yu, Mei Kuen; O’Laughlin, Micheal; Wise, Helen; Chen, Di; Tian, Li; Shi, Dufang; Wang, Jiali; Chen, Sihui; Feng, Jian Q; Chow, Dick Ho Kiu; Xie, Xinhui; Zheng, Lizhen; Huang, Le; Huang, Shuo; Leung, Kwoksui; Lu, Na; Zhao, Lan; Li, Huafang; Zhao, Dewei; Guo, Xia; Chan, Kaiming; Witte, Frank; Chan, Hsiao Chang; Zheng, Yufeng; Qin, Ling

2017-01-01

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL-and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics. PMID:27571347

Behavioral and Physiological Analyses of Parturition In Pregnant Rats: Insights Derived from Intrauterine Telemetry

NASA Technical Reports Server (NTRS)

Villareal, J.; Mallery, E.; Lynch, A.; Mills, N.; Baer, L.; Wade, C.; Ronca, A.; Dalton, Donnie (Technical Monitor)

2002-01-01

During labor and birth, fetuses are exposed to considerable physical stimulation associated with labor contractions and expulsion from the womb These forces are important for the neonates' adaptation to tile extrauterine environment. To further our understanding of the relationship between labor and postpartum outcome, we developed a novel method for measuring intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats that enables us to make precise, reliable measures of the forces experienced by rat fetuses during parturition. A small (1.25 x 4 cm) telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day (G) 19 of the rats' 22/23 day pregnancy, each dam was anesthetized and a balloon/sensor unit surgically implanted within the uterus following removal of two fetuses. Comparisons were made between sensor-implanted dams (IMPL) and a control conditions: 1) LAP-R, laparotomy with two fetuses removed or 2) LAP-NR, laparotomy with no fetuses removed. IUP signals were sampled at 10s intervals from the IMPL dams during labor and birth. Dams in all three conditions were videorecorded enabling us to analyze the effect of the implant on behavioral expressions of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured from one hour prior to the first pup birth until the birth of the third pup were unaffected by the sensor implant. Intrauterine telemetry of freely-moving dams offers significant advantages over conventional hardwired IUP measurement techniques. These findings establish and validate intrauterine telemetry as a reliable, non-invasive technique for quantifying pressures associated with parturition.

Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model.

PubMed

Hata, Junya; Satoh, Yuichi; Akaihata, Hidenori; Hiraki, Hiroyuki; Ogawa, Soichiro; Haga, Nobuhiro; Ishibashi, Kei; Aikawa, Ken; Kojima, Yoshiyuki

2016-07-01

To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model. Fetal urogenital sinus isolated from 20-day-old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time-dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole-genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation). Microarray analyses showed 926 upregulated (>2-fold change, P < 0.01) and 3217 downregulated genes (<0.5-fold change, P < 0.01) in benign prostatic hyperplasia specimens compared with normal prostate. Gene ontology analyses of upregulated genes showed predominant genetic themes of involvement in development (162 genes, P = 2.01 × 10(-4) ), response to stimulus (163 genes, P = 7.37 × 10(-13) ) and growth (32 genes, P = 1.93 × 10(-5) ). When we used both normal prostate and non-transplanted urogenital sinuses as controls to identify benign prostatic hyperplasia-specific genes, 507 and 406 genes were upregulated and downregulated, respectively. Functional network and pathway analyses showed that genes associated with apoptosis modulation by heat shock protein 70, interleukin-1, interleukin-2 and interleukin-5 signaling pathways, KIT signaling pathway, and secretin-like G-protein-coupled receptors, class B, were relatively activated during the growth process in the benign prostatic hyperplasia specimens. In contrast, genes associated with cholesterol biosynthesis were relatively inactivated. Our microarray analyses of the benign prostatic hyperplasia model rat might aid in clarifying the molecular mechanism of benign prostatic hyperplasia progression, and identifying molecular targets for benign prostatic hyperplasia treatment. © 2016 The Japanese Urological Association.

Maintained functionality of an implantable radiotelemetric blood pressure and heart rate sensor after magnetic resonance imaging in rats.

PubMed

Nölte, I; Gorbey, S; Boll, H; Figueiredo, G; Groden, C; Lemmer, B; Brockmann, M A

2011-12-01

Radiotelemetric sensors for in vivo assessment of blood pressure and heart rate are widely used in animal research. MRI with implanted sensors is regarded as contraindicated as transmitter malfunction and injury of the animal may be caused. Moreover, artefacts are expected to compromise image evaluation. In vitro, the function of a radiotelemetric sensor (TA11PA-C10, Data Sciences International) after exposure to MRI up to 9.4 T was assessed. The magnetic force of the electromagnetic field on the sensor as well as radiofrequency (RF)-induced sensor heating was analysed. Finally, MRI with an implanted sensor was performed in a rat. Imaging artefacts were analysed at 3.0 and 9.4 T ex vivo and in vivo. Transmitted 24 h blood pressure and heart rate were compared before and after MRI to verify the integrity of the telemetric sensor. The function of the sensor was not altered by MRI up to 9.4 T. The maximum force exerted on the sensor was 273 ± 50 mN. RF-induced heating was ruled out. Artefacts impeded the assessment of the abdomen and thorax in a dead rat, but not of the head and neck. MRI with implanted radiotelemetric sensors is feasible in principal. The tested sensor maintains functionality up to 9.4 T. Artefacts hampered abdominal and throacic imaging in rats, while assessment of the head and neck is possible.

A novel surgical technique for a rat subcutaneous implantation of a tissue engineered scaffold

PubMed Central

Khorramirouz, Reza; Go, Jason L.; Noble, Christopher; Jana, Soumen; Maxson, Eva; Lerman, Amir; Young, Melissa D.

2018-01-01

Objectives Subcutaneous implantations in small animal models are currently required for preclinical studies of acellular tissue to evaluate biocompatibility, including host recellularization and immunogenic reactivity. Methods Three rat subcutaneous implantation methods were evaluated in six Sprague Dawley rats. An acellular xenograft made from porcine pericardium was used as the tissue-scaffold. Three implantation methods were performed; 1) Suture method is where a tissue-scaffold was implanted by suturing its border to the external oblique muscle, 2) Control method is where a tissue-scaffold was implanted without any suturing or support, 3) Frame method is where a tissue-scaffold was attached to a circular frame composed of polycaprolactone (PCL) biomaterial and placed subcutaneously. After 1 and 4 weeks, tissue-scaffolds were explanted and evaluated by hematoxylin and eosin (H&E), Masson’s trichrome, Picrosirius Red, transmission electron microscopy (TEM), immunohistochemistry, and mechanical testing. Results Macroscopically, tissue-scaffold degradation with the suture method and tissue-scaffold folding with the control method were observed after 4 weeks. In comparison, the frame method demonstrated intact tissue scaffolds after 4 weeks. H&E staining showed progressive cell repopulation over the course of the experiment in all groups with acute and chronic inflammation observed in suture and control methods throughout the duration of the study. Immunohistochemistry quantification of CD3, CD 31, CD 34, CD 163, and αSMA showed a statistically significant differences between the suture, control and frame methods (P < 0.05) at both time points. The average tensile strength was 4.03 ± 0.49, 7.45 ± 0.49 and 5.72 ± 1.34 (MPa) after 1 week and 0.55 ± 0.26, 0.12 ± 0.03 and 0.41 ± 0.32 (MPa) after 4 weeks in the suture, control, and frame methods; respectively. TEM analysis showed an increase in inflammatory cells in both suture and control methods following implantation. Conclusion Rat subcutaneous implantation with the frame method was performed with success and ease. The surgical approach used for the frame technique was found to be the best methodology for in vivo evaluation of tissue engineered acellular scaffolds, where the frame method did not compromise mechanical strength, but it reduced inflammation significantly. PMID:29519681

In vitro characterization of peptide-modified p(AAm-co-EG/AAc) IPN-coated titanium implants.

PubMed

Barber, Thomas A; Gamble, Lara J; Castner, David G; Healy, Kevin E

2006-07-01

Interpenetrating polymer networks (IPNs) of poly(acrylamide-co-ethylene glycol/acrylic acid) [p(AAm-co-EG/AAc)] functionalized with an -Arg-Gly-Asp- containing peptide derived from rat bone sialoprotein [bsp-RGD(15)] were grafted to titanium implants in an effort to modulate osteoblast behavior in vitro. Surface characterization data were consistent with the presence of an IPN, and ligand density measurements established that the range of peptide density on the modified implants spanned three orders of magnitude (0.01-20 pmol/cm2). In vitro biological characterization of the modified implants employing the primary rat calvarial osteoblast (RCO) model resulted in the identification of a critical ligand density (0.01

The Role of the Component Metals in the Toxicity of Military-Grade Tungsten Alloy

PubMed Central

Emond, Christy A.; Vergara, Vernieda B.; Lombardini, Eric D.; Mog, Steven R.; Kalinich, John F.

2015-01-01

Tungsten-based composites have been recommended as a suitable replacement for depleted uranium. Unfortunately, one of these mixtures composed of tungsten (W), nickel (Ni) and cobalt (Co) induced rhabdomyosarcomas when implanted into the leg muscle of laboratory rats and mice to simulate a shrapnel wound. The question arose as to whether the neoplastic effect of the mixture could be solely attributed to one or more of the metal components. To investigate this possibility, pellets with one or two of the component metals replaced with an identical amount of the biologically-inert metal tantalum (Ta) were manufactured and implanted into the quadriceps of B6C3F1 mice. The mice were followed for two years to assess potential adverse health effects. Implantation with WTa, CoTa or WNiTa resulted in decreased survival, but not to the level reported for WNiCo. Sarcomas in the implanted muscle were found in 20% of the CoTa-implanted mice and 5% of the WTa- and WCoTa-implanted rats and mice, far below the 80% reported for WNiCo-implanted mice. The data obtained from this study suggested that no single metal is solely responsible for the neoplastic effects of WNiCo and that a synergistic effect of the three metals in tumor development was likely. PMID:29051474

In vivo magnetic resonance imaging of type I collagen scaffold in rat: improving visualization of bladder and subcutaneous implants.

PubMed

Sun, Yi; Geutjes, Paul; Oosterwijk, Egbert; Heerschap, Arend

2014-12-01

Noninvasive monitoring of implanted scaffolds is important to understand their behavior and role in tissue engineering, in particular to follow their degradation and interaction with host tissue. Magnetic resonance imaging (MRI) is well suited for this goal, but its application is often hampered by the low contrast of scaffolds that are prepared from biomaterials such as type I collagen. The aim of this study was to test iron oxide particles incorporation in improving their MRI contrasts, and to follow their degradation and tissue interactions. Scaffolds with and without iron oxide particles were implanted either subcutaneously or on the bladder of rats. At predetermined time points, in vivo MRI were obtained and tissues were then harvested for histology analysis and transmission electron microscopy. The result showed that the incorporation of iron oxide particles improved MRI contrast of the implants, providing information on their location, shapes, and degradation. Second, the host tissue reaction to the type I collagen implants could be observed in both MRI and histology. Finally, MRI also revealed that the degradation and host tissue reaction of iron particles-loaded scaffolds differed between subcutaneous and bladder implantation, which was substantiated by histology.

Analysis of metallic traces from the biodegradation of endomedullary AZ31 alloy temporary implants in rat organs after long implantation times.

PubMed

Bodelón, O G; Iglesias, C; Garrido, J; Clemente, C; Garcia-Alonso, M C; Escudero, M L

2015-08-04

AZ31 alloy has been tested as a biodegradable material in the form of endomedullary implants in female Wistar rat femurs. In order to evaluate the accumulation of potentially toxic elements from the biodegradation of the implant, magnesium (Mg), aluminium (Al), zinc (Zn), manganese (Mn) and fluorine (F) levels have been measured in different organs such as kidneys, liver, lungs, spleen and brain. Several factors that may influence accumulation have been taken into account: how long the implant has been in place, whether or not the bone is fractured, and the presence of an MgF2 protective coating on the implant. The main conclusions and the clinical relevance of the study have been that AZ31 endomedullary implants have a degradation rate of about 60% after 13 months, which is fully compatible with fracture consolidation. Neither bone fracture nor an MgF2 coating seems to influence the accumulation of trace elements in the studied organs. Aluminium is the only alloying element in this study that requires special attention. The increase in Al recovered from the sampled organs represents 3.95% of the amount contained in the AZ31 implant. Al accumulates in a statistically significant way in all the organs except the brain. All of this suggests that in long-term tests AZ31 may be a suitable material for osteosynthesis.

Long-term inflammatory response to liquid injectable silicone, cartilage, and silicone sheet.

PubMed

Hizal, Evren; Buyuklu, Fuat; Ozdemir, B Handan; Erbek, Selim S

2014-11-01

To show and compare the long-term inflammatory responses to subdermal microdroplet injections of 1,000 centistoke (cS) and 5,000 cS liquid injectable silicone (LIS), and to assess the applicability of insulin pen as an alternative LIS delivery device in an animal model. Animal study. Eighteen healthy adult Sprague-Dawley rats were used. Two graft recipient sites and four injection sites were prepared on each rat's back for: 1) autogenous auricular cartilage graft; 2) silicone sheet; 3) 1,000 cS LIS injection with insulin syringe; 4) 1,000 cS LIS injection with insulin pen; 5) 5,000 cS LIS injection with insulin syringe; and 6) 5,000 cS LIS injection with insulin pen. The animals were followed up for 6 months, and skin biopsies were examined for the evaluation of LIS microdroplets in situ and the degree of inflammatory tissue response. Immunohistochemistry was used for the examination of macrophages and the density of microvessels. Biopsies from 17 animals were assessed. There was no statistically significant difference among the groups in terms of the number of lymphocytes (P = 0.081), macrophages (P = 0.857), and neutrophils (P = 0.995), the degree of vascular proliferation (P = 0.698), and the mean LIS microdroplet diameter (P = 0.540). Grossly, there was no sign of granuloma formation in any of the specimens. There is a low-grade, well-tolerated long-term inflammatory response to microdroplet injections of 1,000 cS and 5,000 cS LIS that is comparable to autogenous cartilage graft in rats. Standard dose delivery devices such as insulin pens can be used for controlled LIS injections. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Altered brainstem auditory evoked potentials in a rat central sensitization model are similar to those in migraine

PubMed Central

Arakaki, Xianghong; Galbraith, Gary; Pikov, Victor; Fonteh, Alfred N.; Harrington, Michael G.

2014-01-01

Migraine symptoms often include auditory discomfort. Nitroglycerin (NTG)-triggered central sensitization (CS) provides a rodent model of migraine, but auditory brainstem pathways have not yet been studied in this example. Our objective was to examine brainstem auditory evoked potentials (BAEPs) in rat CS as a measure of possible auditory abnormalities. We used four subdermal electrodes to record horizontal (h) and vertical (v) dipole channel BAEPs before and after injection of NTG or saline. We measured the peak latencies (PLs), interpeak latencies (IPLs), and amplitudes for detectable waveforms evoked by 8, 16, or 32 KHz auditory stimulation. At 8 KHz stimulation, vertical channel positive PLs of waves 4, 5, and 6 (vP4, vP5, and vP6), and related IPLs from earlier negative or positive peaks (vN1-vP4, vN1-vP5, vN1-vP6; vP3-vP4, vP3-vP6) increased significantly 2 hours after NTG injection compared to the saline group. However, BAEP peak amplitudes at all frequencies, PLs and IPLs from the horizontal channel at all frequencies, and the vertical channel stimulated at 16 and 32 KHz showed no significant/consistent change. For the first time in the rat CS model, we show that BAEP PLs and IPLs ranging from putative bilateral medial superior olivary nuclei (P4) to the more rostral structures such as the medial geniculate body (P6) were prolonged 2 hours after NTG administration. These BAEP alterations could reflect changes in neurotransmitters and/or hypoperfusion in the midbrain. The similarity of our results with previous human studies further validates the rodent CS model for future migraine research. PMID:24680742

Effects of aloe vera gel on the induction of endometriosis and regression of endometrial explants in a rat model.

PubMed

Bostanci, M S; Bakacak, M; Kizilkale Yildirim, O; Yildirim, G; Attar, R; Özkan, F; Inanc Tolun, F

2016-01-01

To evaluate the preventive and reducing effect of aloe vera gel on surgically-induced endometrial foci in rats. Twenty-four reproductive aged female non-pregnant, nulligravid Sprague-Dawley albino rats were used. The rats were randomly divided to three groups (Group 1: control, Group 2: aloe vera endometriosis formation, and Group 3: aloe vera endometriosis treatment). A peritoneal lavage using one-ml saline was taken at all the operations for determination of superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT). Forty-eight horns were implanted in 24 rats. All the implants were properly formed after implantation. In Group 3, before aloe vera application, the sum of the volumes was 87.2 ± 20.4 mm³ and after treatment the volumes dropped to 28.9 ± 14.9 mm3 (p = 0.01). As evaluation of aloe vera on the formation of endometriosis in the second operation in Group 2, the sum of the volumes was 2.9±1.4 mm³ and in Group 1, 118.9 ± 20.0 mm3 (p = 0.001). Likewise, similar changes were observed in the histopatological scores. The application of aloe vera was seen to raise antioxidant levels in the peritoneal fluid and to reduce oxidative stress markers. Aloe vera is effective in the inhibition of formation and regression of endometriotic lesions.

A Cell-Adhesive Plasma Polymerized Allylamine Coating Reduces the In Vivo Inflammatory Response Induced by Ti6Al4V Modified with Plasma Immersion Ion Implantation of Copper

PubMed Central

Walschus, Uwe; Hoene, Andreas; Patrzyk, Maciej; Lucke, Silke; Finke, Birgit; Polak, Martin; Lukowski, Gerold; Bader, Rainer; Zietz, Carmen; Podbielski, Andreas; Nebe, J. Barbara; Schlosser, Michael

2017-01-01

Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film (PPAAm). Thus, this study aimed to examine in vivo local inflammatory reactions for Ti6Al4V implants treated with Cu-PIII (Ti-Cu), alone or with an additional PPAAm film (Ti-Cu-PPAAm), compared to untreated implants (Ti). Successful Cu-PIII and PPAAm treatment was confirmed with X-ray Photoelectron Spectroscopy. Storage of Ti-Cu and Ti-Cu-PPAAm samples in double-distilled water for five days revealed a reduction of Cu release by PPAAm. Subsequently, Ti, Ti-Cu and Ti-Cu-PPAAm samples were simultaneously implanted into the neck musculature of 24 rats. After 7, 14 and 56 days, peri-implant tissue was retrieved from 8 rats/day for morphometric immunohistochemistry of different inflammatory cells. On day 56, Ti-Cu induced significantly stronger reactions compared to Ti (tissue macrophages, antigen-presenting cells, T lymphocytes) and to Ti-Cu-PPAAm (tissue macrophages, T lymphocytes, mast cells). The response for Ti-Cu-PPAAm was comparable with Ti. In conclusion, PPAAm reduced the inflammatory reactions caused by Cu-PIII. Combining both plasma processes could be useful to create antibacterial and tissue compatible Ti-based implants. PMID:28726761

Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.

PubMed

Maruyama, Takashi; Fukuda, Noboru; Matsumoto, Taro; Kano, Koichiro; Endo, Morito; Kazama, Minako; Kazama, Tomohiko; Ikeda, Jin; Matsuda, Hiroyuki; Ueno, Takahiro; Abe, Masanori; Okada, Kazuyoshi; Soma, Masayoshi; Matsumoto, Koichi; Kawachi, Hiroshi

2015-04-16

Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein. Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guilmette, Ray A.; Hahn, Fletcher F.; Durbin, P. W.

A number of U. S. veterans of the Persian Gulf War were wounded with depleted uranium (DU) metal fragments as a result of 'friendly fire' incidents, in which Abrams tanks and Bradley fighting vehicles were struck by DU anti-armor munitions. Some of the crew members who survived were left with multiple small fragments of DU in their muscles and soft tissues. The number, size and location of the fragments made them inoperable in general, and therefore subject to long-term retention. Because there was inadequate data to predict the potential carcinogenicity of DU fragments in soft tissues, Hahn et al. (2003)more » conducted a lifespan cancer study in rats. As part of that study, a number of rats were maintained to study the biokinetics and dosimetry of DU implanted intramuscularly in male Wistar rats. Typically, four metal fragments, either as cylindrical pellets or square wafers were implanted into the biceps femoris muscles of the rats. Urine samples were collected periodically during their lifespans, and DU was analyzed in kidneys and eviscerated carcass (minus the implant sites) at death. The daily DU urinary excretion rate increased steeply during the first 30 d after implantation peaking at about 90 d at 3-10 x 10{sup -3}%/d. During the first 150 d, the average excretion rate was 2.4 x 10{sup -3}%/d, decreasing thereafter to about 1 x 10{sup -3}%/d. Serial radiographs were made of the wound sites to monitor gross morphologic changes in the DU implant and the surrounding tissue. As early as 1 w after implantation, radiographs showed the presence of surface corrosion and small, dense bodies near the original implant, presumably DU. This corrosion from the surface of the implant continued with time, but did not result in an increasing amount of DU reaching the blood and urine after the first 3 mo. During this 3-mo period, connective tissue capsules formed around the implants, and are hypothesized to have reduced the access of DU to tissue fluids by limiting the diffusion rate of dissolved chemical forms of DU. Using a model of wound-site retention being developed by a committee of the U.S. National Council of Radiation Protection and Measurements (NCRP), it was found that the average retention of DU in the wound site could be described by a two-component exponential function in which 0.5% of the DU was retained with a half time of 80 d and the remainder with a half time of about 300 y.« less

Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation

PubMed Central

2014-01-01

Background Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. Methods We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. Results Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. Conclusion Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy. PMID:24758405

Histological and histomorphometrical analysis of a silica matrix embedded nanocrystalline hydroxyapatite bone substitute using the subcutaneous implantation model in Wistar rats.

PubMed

Ghanaati, Shahram; Orth, Carina; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin W; Booms, Patrick; Stübinger, Stefan; Landes, Constantin; Sader, Robert Anton; Kirkpatrick, Charles James

2010-06-01

The clinical suitability of a bone substitute material is determined by the ability to induce a tissue reaction specific to its composition. The aim of this in vivo study was to analyze the tissue reaction to a silica matrix-embedded, nanocrystalline hydroxyapatite bone substitute.The subcutaneous implantation model in Wistar rats was chosen to assess the effect of silica degradation on the vascularization of the biomaterial and its biodegradation within a time period of 6 months. Already at day 10 after implantation, histomorphometrical analysis showed that the vascularization of the implantation bed reached its peak value compared to all other time points. Both vessel density and vascularization significantly decreased until day 90 after implantation. In this time period, the bone substitute underwent a significant degradation initiated by TRAP-positive and TRAP-negative multinucleated giant cells together with macrophages and lymphocytes. Although no specific tissue reaction could be related to the described silica degradation, the biomaterial was close to being fully degraded without a severe inflammatory response. These characteristics are advantageous for bone regeneration and remodeling processes.

Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity

PubMed Central

2004-01-01

Few cell adhesion molecules have been reported to be expressed in mature adipocytes, and the significance of cell adhesion process in adipocyte biology is also unknown. In the present study, we identified ACAM (adipocyte adhesion molecule), a novel homologue of the CTX (cortical thymocyte marker in Xenopus) gene family. ACAM cDNA was isolated during PCR-based cDNA subtraction, and its mRNA was shown to be up-regulated in WATs (white adipose tissues) of OLETF (Otsuka Long–Evans Tokushima fatty) rats, an animal model for Type II diabetes and obesity. ACAM, 372 amino acids in total, has a signal peptide, V-type (variable) and C2-type (constant) Ig domains, a single transmembrane segment and a cytoplasmic tail. The amino acid sequence in rat is highly homologous to mouse (94%) and human (87%). ACAM mRNA was predominantly expressed in WATs in OLETF rats, and increased with the development of obesity until 30 weeks of age, which is when the peak of body mass is reached. Western blot analysis revealed that ACAM protein, approx. 45 kDa, was associated with plasma membrane fractions of mature adipocytes isolated from mesenteric and subdermal adipose deposits of OLETF rats. Up-regulation of ACAM mRNAs in obesity was also shown in WATs of genetically obese db/db mice, diet-induced obese ICR mice and human obese subjects. In primary cultured mouse and human adipocytes, ACAM mRNA expression was progressively up-regulated during differentiation. Several stably transfected Chinese-hamster ovary K1 cell lines were established, and the quantification of ACAM mRNA and cell aggregation assay revealed that the degree of homophilic aggregation correlated well with ACAM mRNA expression. In summary, ACAM may be the critical adhesion molecule in adipocyte differentiation and development of obesity. PMID:15563274

PRE AND POST-IMPLANTATION CHANGES IN THE UTEUS OF RATS: RESPONSE TO MORINGA OLEIFERA LAM. EXTRACT

PubMed Central

Prakash, Anand O.; Pathak, Sandhya; Shukla, Sangeeta; Mathur, R.

1988-01-01

Aqueous extract of Moringa oleifera Lam. (root) has been studies on pre and post-implementation stages of the uterus of rats so as to elucidate its antifertility mode of action. Results on the biochemical estimation in the uterus of control pregnant rats at different stages of pregnancy revealed a successive increase in the total proteins, glycogen content and the activity or acid and alkaline phosphatase from day 2 to 5 post-coitum. When aqueous extract of M. oleifera Lam. Was administered, there was a significant reduction in all these biochemical constituents when compared to their respective control groups. The role of these biochemical transformations has been discussed in relation to anti-implantation action of the extract. PMID:22557630

Magnetic stem cell targeting to the inner ear

NASA Astrophysics Data System (ADS)

Le, T. N.; Straatman, L.; Yanai, A.; Rahmanian, R.; Garnis, C.; Häfeli, U. O.; Poblete, T.; Westerberg, B. D.; Gregory-Evans, K.

2017-12-01

Severe sensorineural deafness is often accompanied by a loss of auditory neurons in addition to injury of the cochlear epithelium and hair cell loss. Cochlear implant function however depends on a healthy complement of neurons and their preservation is vital in achieving optimal results. We have developed a technique to target mesenchymal stem cells (MSCs) to a deafened rat cochlea. We then assessed the neuroprotective effect of systematically delivered MSCs on the survival and function of spiral ganglion neurons (SGNs). MSCs were labeled with superparamagnetic nanoparticles, injected via the systemic circulation, and targeted using a magnetized cochlea implant and external magnet. Neurotrophic factor concentrations, survival of SGNs, and auditory function were assessed at 1 week and 4 weeks after treatments and compared against multiple control groups. Significant numbers of magnetically targeted MSCs (>30 MSCs/section) were present in the cochlea with accompanied elevation of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor levels (p < 0.001). In addition we saw improved survival of SGNs (approximately 80% survival at 4 weeks). Hearing threshold levels in magnetically targeted rats were found to be significantly better than those of control rats (p < 0.05). These results indicate that magnetic targeting of MSCs to the cochlea can be accomplished with a magnetized cochlear permalloy implant and an external magnet. The targeted stem cells release neurotrophic factors which results in improved SGN survival and hearing recovery. Combining magnetic cell-based therapy and cochlear implantation may improve cochlear implant function in treating deafness.

Heparin-binding growth factor 1 induces the formation of organoid neovascular structures in vivo.

PubMed Central

Thompson, J A; Haudenschild, C C; Anderson, K D; DiPietro, J M; Anderson, W F; Maciag, T

1989-01-01

One of the promises of modern molecular biology has been the opportunity to use genetically modified human cells in a patient to permanently restore inborn errors of metabolism. Although it has been possible to introduce genes into mammalian cells and to control their expression, it has proven difficult to introduce mammalian cells as carriers of the modified genetic information into hosts. The successful implantation of selective cells cannot be achieved without adequate vascular support, an essential step toward integration and reconstitution of a new biological function. Although a partial solution to this problem has been found by inducing specific site-directed neovessel formation using heparin-binding growth factor 1 (HBGF-1) adsorbed to a collagen matrix, these implants function for only a short period (weeks). We now report the formation of organoid neovascular structures using polytetrafluoroethylene fibers coated with collagen and HBGF-1 implanted in the peritoneal cavity of the rat. The organoid structures contained readily visible vascular lumina and nonvascular structures that resemble nerve tissue. It was also possible to demonstrate that the vascular system on the implant is continuous with the vascular tree of the host. This feature was used to demonstrate that the organoid structures are capable of sustaining the biological function of implanted normal rat hepatocytes over long periods of time (months) in the homozygous Gunn rat, thereby facilitating future applications involving the delivery of new genetic information. Images PMID:2479012

Does the design of mini slings anchoring systems really matter? A biomechanical comparison between Mini Arc™ and Ophira™.

PubMed

Santos-Souza, R; Rodrigues-Palma, P C; Goulart-Fernandes-Dias, F; Teixeira-Siniscalchi, R; Zanettini-Riccetto, C L

2016-11-01

Currently, a sling implant is the standard treatment for stress urinary incontinence in women. To be effective, they require an adequate anchoring system. The aim of this study is compare biomechanical features of fixation systems of two mini slings models available on the market (Ophira™ and Mini Arc™) through a tensile test. Anchoring devices of each sling were surgically implanted in abdominal wall of 15 rats divided into three groups of five animals which were arranged according to the date of post implant euthanasia on 7, 14 and 30 days. Abdominal walls of rats were extracted on bloc containing the anchoring system and were submitted to a tensile strength test to measure the maximum load and elongation until device avulsion from the tissue. The results were compared using Student test t and a 5% cut off was considered significant. The Ophira™ mini sling fixation system demanded a greater maximum load and developed a longer stretch for avulsion from the implanted site at all moments evaluated (p value less than 0.05). There were significant differences in fixation patterns of the anchoring systems, which were exclusively related to their designs. The Ophira™ mini sling fixation device provided better fixation to the abdominal wall of rats compared to the Mini Arc™ device, even in the late post implant period. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Enhancing of Osseointegration with Propolis-Loaded TiO2 Nanotubes in Rat Mandible for Dental Implants

PubMed Central

Somsanith, Nithideth; Jang, Young-Seok; Lee, Young-Hee; Yi, Ho-Keun; Kim, Kyoung-A; Bae, Tae-Sung; Lee, Min-Ho

2018-01-01

TiO2 nanotubes (TNT) formation is beneficial for improving bone cell–material interaction and drug delivery for Ti dental implants. Among the natural drugs to be installed in TNT, selected propolis has antibacterial and anti-inflammatory properties. It is a resinous natural product which is collected by the honeybees from the various types of plants with their salivary enzymes. This study concludes that TNT loaded with a propolis (PL-TNT-Ti) dental implant has the ability to improve osseointegration. The propolis particles were embedded within the TNT or adhered to the top. In a cytotoxicity test using osteoblast, PL-TNT-Ti group exhibited an increased cell proliferation and differentiation. A Sprague Dawley rat mandibular model was used to evaluate the osseointegration and bone bonding of TNT or PL-TNT-Ti. From the µ-CT and hematoxylin and eosin (HE) histological results after implantation at 1 and 4 weeks to rat mandibular, an increase in the extent of new bone formation and mineral density around the PL-TNT-Ti implant was confirmed. The Masson’s trichrome staining showed the expression of well-formed collagenous for bone formation on the PL-TNT-Ti. Immunohistochemistry staining indicate that bone morphogenetic proteins (BMP-2 and BMP-7) around the PL-TNT-Ti increased the expression of collagen fibers and of osteogenic differentiation whereas the expression of inflammatory cytokine such as interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) is decreased. PMID:29301269

Reduced tumorigenicity of rat glioma cells in the brain when mediated by hygromycin phosphotransferase.

PubMed

Hormigo, A; Friedlander, D R; Brittis, P A; Zagzag, D; Grumet, M

2001-04-01

A variant of C6 glioma cells, C6R-G/H cells express hygromycin phosphotransferase (HPT) and appear to have reduced tumorigenicity in the embryonic brain. The goal of this study was to investigate their reduced capacity to generate tumors in the adult rat brain. Cell lines were implanted into rat brains and tumorigenesis was evaluated. After 3 weeks, all rats with C6 cells showed signs of neurological disease, whereas rats with C6R-G/H cells did not and were either killed then or allowed to survive until later. Histological studies were performed to analyze tumor size, malignancy, angiogenesis, and cell proliferation. Cells isolated from rat brain tumors were analyzed for mutation to HPT by testing their sensitivity to hygromycin. The results indicate that HPT suppresses tumor formation. Three weeks after implantation, only 44% of animals implanted with C6R-G/H cells developed tumors, whereas all animals that received C6 glioma cells developed high-grade gliomas. The C6R-G/H cells filled a 20-fold smaller maximal cross-sectional area than the C6 cells, and exhibited less malignant characteristics, including reduced angiogenesis, mitosis, and cell proliferation. Similar results were obtained in the brain of nude rats, indicating that the immune system did not play a significant role in suppressing tumor growth. The combination of green fluorescent protein (GFP) and HPT was more effective in suppressing tumorigenesis than either plasmid by itself, indicating that the GFP may protect against inactivation of the HPT. Interestingly. hygromycin resistance was lost in tumor cells that were recovered from a group of animals in which C6R-G/H cells formed tumors, confirming the correlation of HPT with reduced tumorigenicity.

Testing of Raman spectroscopy method for assessment of skin implants

NASA Astrophysics Data System (ADS)

Timchenko, E. V.; Timchenko, P. E.; Volova, L. T.; Pershutkina, S. V.; Shalkovskaya, P. Y.

2016-11-01

Results of studies of testing of Raman spectroscopy (RS) method for assessment of skin implants are presented. As objects of study were used samples of rat's skin material. The main spectral differences of implants using various types of their processing appear at wavenumbers 1062 cm-1, 1645 cm-1, 1553 cm-1, 851 cm-1, 863 cm-1, 814 cm-1 and 1410 cm-1. Optical coefficients for assessment of skin implants were introduced. The research results are confirmed by morphological analysis.

Regeneration of Musculoskeletal Tissues by Prolonged Low-Grade Inflammation

DTIC Science & Technology

2011-10-01

grade inflammation around a pure collagen based scaffold on implantation into the rabbit patellar tendon. Additionally, the cross-sectional areas of...the tendons treated with the implant were about 40% greater compared to the sham- operated controls. In the current study, we hypothesized that soft...was implanted into the rat patellar tendon using a minimally invasive technique and the inflammation was blocked using liposomal clodronate. The

Superficial Enhanced Fluid Fat Injection (SEFFI) to Correct Volume Defects and Skin Aging of the Face and Periocular Region.

PubMed

Bernardini, Francesco P; Gennai, Alessandro; Izzo, Luigi; Zambelli, Alessandra; Repaci, Erica; Baldelli, Ilaria; Fraternali-Orcioni, G; Hartstein, Morris E; Santi, Pier Luigi; Quarto, Rodolfo

2015-07-01

Although recent research on micro fat has shown the potential advantages of superficial implantation and high stem cell content, clinical applications thus far have been limited. The authors report their experience with superficial enhanced fluid fat injection (SEFFI) for the correction of volume loss and skin aging of the face in general and in the periocular region. The finer SEFFI preparation (0.5 mL) was injected into the orbicularis in the periorbital and perioral areas, and the 0.8-mL preparation was injected subdermally elsewhere in the face. The records of 98 consecutive patients were reviewed. Average follow-up time was 6 months, and average volume of implanted fat was 20 mL and 51.4 mL for the 0.5-mL and 0.8-mL preparations, respectively. Good or excellent results were achieved for volume restoration and skin improvement in all patients. Complications were minor and included an oil cyst in 3 patients. The smaller SEFFI quantity (0.5 mL) was well suited to correct volume loss in the eyelids, especially the deep upper sulcus and tear trough, whereas the larger SEFFI content was effective for larger volume deficits in other areas of the face, including the brow, temporal fossa, zygomatic-malar region, nasolabial folds, marionette lines, chin, and lips. The fat administered by SEFFI is easily harvested via small side-port cannulae, yielding micro fat that is rich in viable adipocytes and stem cells. Both volumes of fat (0.5 mL and 0.8 mL) were effective for treating age-related lipoatrophy, reducing facial rhytids, and improving skin quality. 4 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Contraception Insurance Coverage and Receipt of Long-Acting Reversible Contraception or Depot Medroxyprogesterone Acetate on the Day of Abortion.

PubMed

Krashin, Jamie W; Stuart, Gretchen S; Garrett, Joanne; Spector, Hannah; Bryant, Amy G; Charm, Samantha; Morse, Jessica E

2017-07-01

To evaluate whether contraceptive insurance coverage for women who present for an abortion is associated with obtaining long-acting reversible contraception or depot medroxyprogesterone acetate (DMPA) on the day the abortion is completed. We conducted a prospective cohort study of women presenting for medical or surgical abortion at a single health center in North Carolina. Eligible women were 18 years or older and fluent in English or Spanish. Data were from participant questionnaires, medical charts, and financial records. Our main exposure was whether the woman had insurance coverage for contraception at clinic intake. Our primary outcome was receiving DMPA, an intrauterine device, or a contraceptive subdermal implant on the same day of their surgical abortion or at the visit that determined their medication abortion was complete. We used univariable, bivariable, and multivariable analysis to report our findings. Five hundred seventy-five women enrolled in our cohort between September 2015 and April 2016. One hundred twenty-eight (22%) had insurance coverage and 447 (78%) did not. In the group with insurance coverage for contraception, 38% (49/128) received a long-acting reversible contraception method or DMPA compared with 7% (33/447) in the group without insurance coverage for contraception. After adjusting for confounding, women with contraceptive coverage were more than five times as likely to receive immediate postabortion contraception with one of these methods compared with women without coverage (relative risk 5.6, 95% confidence interval 3.8-8.3). Women with contraceptive insurance coverage on the day of their abortion were more likely to leave the abortion clinic with an intrauterine device or implant in place or receive DMPA injection compared with women without coverage.

Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

PubMed

Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

2014-07-08

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

An improved method of electrode placement in configuration Lead II for the reliable ECG recording by telemetry in the conscious rat.

PubMed

Tontodonati, Marcello; Fasdelli, Nicola; Dorigatti, Roberto

2011-01-01

Telemetry represents the gold standard technique for the acquisition of animal haemodynamic signals in the pharmaceutical preclinical development of new chemical entities. In terms of electrocardiographic signal recording, the quality is well established in large animals, mainly dog, non human primates and minipig, whereas it is still lacking in terms of satisfactory results in rodents (mouse and rat in particular). In very recent times, an increasing interest in early safety prediction for the reduction of cardiovascular attrition has been raised in all the major pharmaceutical companies, focusing in particular, on in vivo models. Crl:CD(SD) and Wistar Han rats (Crl:WI[Han], Charles River) underwent surgery for the implantation of telemetry devices (Data Science International, USA) for the acquisition of blood pressure and electrocardiogram (ECG). A group of male CD rats (N=6) was implanted using the standard procedure as described by DSI technical documentation; another male CD group (N=3) was implanted using the technique described by Sgoifo et al. (1996); a third group (total of N=46, N=26 male CD rats, and N=10 male WI and N=10 female WI) was implanted using an alternative approach developed in our laboratory. The new surgical procedure was analysed based on technical difficulties, time to complete the surgery, time to recover, animal care, survival time after surgery and quality of telemetry signal recordings. Although a quantitative and qualitative comparison with other techniques described in literature was beyond the scope of the present work, based on our laboratory experience, Sgoifo's methodology showed better results compared to DSI standard approach, but surgical procedure was not easy to perform and more invasive. The novel approach described in the present paper was characterised by simplicity, repeatability, high rate of survival and improved quality of ECG signals for all the implanted rats. Telemetry in small rodents became of particular interest in the early safety assessment of cardiovascular liability during the development of new chemical entities. Although several surgical procedures are well described in literature, none seem to offer high standard electrocardiography signals in order to reliably detect intervals or arrhythmias. In the Safety Pharmacology Laboratory at GlaxoSmithKline, Verona (Italy), a novel and alternative surgical placement of the electrocardiographic electrodes in Lead II configuration was developed, in the rat. The scope of the present paper is to illustrate that this alternative surgical procedure is easily reproducible, minimally invasive and gives high standard quality ECG signals. Copyright © 2010 Elsevier Inc. All rights reserved.

One year Rat Study of iBTA-induced "Microbiotube" Microvascular Grafts With an Ultra-Small Diameter of 0.6 mm.

PubMed

Ishii, Daizo; Enmi, Jun-Ichiro; Iwai, Ryosuke; Kurisu, Kaoru; Tatsumi, Eisuke; Nakayama, Yasuhide

2018-06-01

The world's smallest calibre "microbiotube" vascular graft was recently developed, with an inner diameter of 0.6 mm. It was formed using in-body tissue architecture (iBTA) and has a high degree of patency and capacity for regeneration in the acute phase, 1 month after implantation. This consecutive study investigated the compatibility and stability of microbiotubes in the chronic phase of implantation for 12 months for potential application in microsurgery. This was an in vivo experimental study. The microbiotubes were prepared by embedding the mould subcutaneously in rats for 2 months. Allogenic microbiotubes (n = 16) were implanted into the bilateral femoral arteries (inner diameter 0.5 mm) of eight Wistar rats in an end to end anastomosis manner for 12 months. Follow up 7-Tesla magnetic resonance angiograms were performed every 3 months. Histological observation was performed 12 months after implantation. All patent grafts (n = 12, patency 75%) one month after implantation maintained their patency up to 12 months without any abnormal morphological changes or calcification. Histological observation at 12 months showed that layered α-smooth muscle actin positive cells with a monolayer luminal covering of endothelial cells had formed from the proximal to the distal anastomoses. A thin elastic fibre layer formed in the luminal area. After implantation, all components of the microbiotube were similar to those of a native artery. This study suggests that microbiotubes have high compatibility, stability, and durability as replacement grafts over the short to mid-term period. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Effects of NMDA and non-NMDA ionotropic glutamate receptors in the medial preoptic area on body temperature in awake rats.

PubMed

Sengupta, Trina; Jaryal, Ashok Kumar; Mallick, Hruda Nanda

2016-10-01

Glutamate when microinjected at the medial preoptic area (mPOA) influences brain temperature (T br ) and body temperature (T b ) in rats. Glutamate and its various receptors are present at the mPOA. The aim of this study was to identify the contribution of each of the ionotropic glutamatergic receptors at the mPOA on changes in T br and T b in freely moving rats. Adult male Wistar rats (n=40) were implanted with bilateral guide cannula with indwelling styli above the mPOA. A telemetric transmitter was implanted at the peritoneum to record T b and locomotor activity (LMA). A precalibrated thermocouple wire implanted near the hypothalamus was used to assess T br . Specific agonist for each ionotropic glutamate receptor was microinjected into the mPOA and its effects on temperature and LMA were measured in the rats. The rats were also microinjected with the respective ionotropic receptor antagonists, 15min prior to the microinjection of each agonist. Amongst amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA) and kainic acid, AMPA increased T b and LMA when injected at the mPOA. Specific antagonists for AMPA receptors was able to attenuate this increase (p<0.005). Pharmacological blockade of NMDA was able to lower T br only. Microinjection of kainic acid and its antagonist had no effect on the variables. The finding of the study suggests that activation of the AMPA receptors at the mPOA, leads to the rise in body temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

PubMed

Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

2001-01-01

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

Attenuation of Activity in an Endogenous Analgesia Circuit by Ongoing Pain in the Rat

PubMed Central

Ferrari, Luiz F.; Gear, Robert W.; Levine, Jon D.

2010-01-01

Analgesic efficacy varies depending on the pain syndrome being treated. One reason for this may be a differential effect of individual pain syndromes on the function of endogenous pain control circuits at which these drugs act to produce analgesia. To test this hypothesis we examined the effects of diverse (i.e., ongoing inflammatory, neuropathic, or chronic widespread) pain syndromes on analgesia induced by activation of an opioid-mediated noxious stimulus-induced endogenous pain control circuit. This circuit was activated by subdermal capsaicin injection at a site remote from the site of nociceptive testing. Analgesia was not affected by carrageenan-induced inflammatory pain nor the early-phase of oxaliplatin neuropathy (a complication of cancer chemotherapy). However, the duration of analgesia was markedly shorter in the late-phase of oxaliplatin neuropathy and in alcoholic neuropathy. A model of fibromyalgia syndrome produced by chronic unpredictable stress and proinflammatory cytokines also shortened analgesia duration, but so did the same stress alone. Therefore, since chronic pain can activate neuroendocrine stress axes, we tested whether they are involved in the attenuation of analgesic duration induced by these pain syndromes. Rats in which the sympathoadrenal axis was ablated by adrenal medullectomy showed normal duration pain-induced analgesia in groups with either late-phase oxaliplatin neuropathy, alcoholic neuropathy, or exposure to sound stress. These results support the suggestion that pain syndromes can modulate activity in endogenous pain control circuits, and this effect is sympathoadrenal dependent. PMID:20943910

Effects of restricted maternal contact in neonatal rats on sexual behaviour in the adult.

PubMed

Forsberg, G; Abrahamsson, K; Södersten, P; Eneroth, P

1985-03-01

Rats, deprived of maternal contact and nutrition every alternate day starting on day 5 of life, attained a body weight at 45 days of age which was 50% of that of rats which had free access to maternal contact and nutrition. After 55 days of unrestricted food availability the body weight of the neonatally deprived rats was approximately 15% lower than that of the controls. Malnourished female rats showed normal behavioural oestrous cycles and became pregnant and lactated normally as young adults. After ovariectomy they showed higher lordosis quotients in response to treatment with oestradiol benzoate and progesterone than controls but lost less body weight in response to treatment with oestradiol-filled constant-release implants. Malnourished male rats ejaculated less frequently than controls in tests with sexually receptive female rats but this difference disappeared with repeated testing. The malnourished males showed longer ejaculation latencies and had somewhat higher serum concentrations of LH than controls after castration and treatment with testosterone-filled constant-release implants which reduced serum androgen concentrations to about 30% of the intact level. The results show that rats are capable of sustaining a rather severe neonatal nutritional deprivation without losing the capacity for essentially normal mating behaviour in adulthood.

Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

PubMed Central

Wu, Hui; Xu, Xiao; Meng, Ying; Xia, Fangzhen; Zhai, Hualing; Lu, Yingli

2014-01-01

Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1) was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo. PMID:24772449

Creating an Animal Model of Tendinopathy by Inducing Chondrogenic Differentiation with Kartogenin.

PubMed

Yuan, Ting; Zhang, Jianying; Zhao, Guangyi; Zhou, Yiqin; Zhang, Chang-Qing; Wang, James H-C

2016-01-01

Previous animal studies have shown that long term rat treadmill running induces over-use tendinopathy, which manifests as proteoglycan accumulation and chondrocytes-like cells within the affected tendons. Creating this animal model of tendinopathy by long term treadmill running is however time-consuming, costly and may vary among animals. In this study, we used a new approach to develop an animal model of tendinopathy using kartogenin (KGN), a bio-compound that can stimulate endogenous stem/progenitor cells to differentiate into chondrocytes. KGN-beads were fabricated and implanted into rat Achilles tendons. Five weeks after implantation, chondrocytes and proteoglycan accumulation were found at the KGN implanted site. Vascularity as well as disorganization in collagen fibers were also present in the same site along with increased expression of the chondrocyte specific marker, collagen type II (Col. II). In vitro studies confirmed that KGN was released continuously from KGN-alginate in vivo beads and induced chondrogenic differentiation of tendon stem/progenitor cells (TSCs) suggesting that chondrogenesis after KGN-bead implantation into the rat tendons is likely due to the aberrant differentiation of TSCs into chondrocytes. Taken together, our results showed that KGN-alginate beads can be used to create a rat model of tendinopathy, which, at least in part, reproduces the features of over-use tendinopathy model created by long term treadmill running. This model is mechanistic (stem cell differentiation), highly reproducible and precise in creating localized tendinopathic lesions. It is expected that this model will be useful to evaluate the effects of various topical treatments such as NSAIDs and platelet-rich plasma (PRP) for the treatment of tendinopathy.

Lumbar spine intervertebral disc gene delivery: a pilot study in lewis rats.

PubMed

Damle, Sheela R; Rawlins, Bernard A; Boachie-Adjei, Oheneba; Crystal, Ronald G; Hidaka, Chisa; Cunningham, Matthew E

2013-02-01

Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc. This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery. Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure. Statistically significant differences were noted for recovery of the β-galactosidase marker gene comparing delivery of naïve or labeled cells (10(5) cells per disc) from the site of implantation, and between delivery of 10(5) or 10(6) labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the β-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation. The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.

Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

NASA Astrophysics Data System (ADS)

Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

Urodynamic measurements reflect physiological bladder function in rats.

PubMed

Schneider, Marc P; Sartori, Andrea M; Tampé, Juliane; Moors, Selina; Engmann, Anne K; Ineichen, Benjamin V; Hofer, Anna-Sophie; Schwab, Martin E; Kessler, Thomas M

2018-04-01

Our objective was to investigate and compare bladder function in rats assessed by metabolic cage and by urodynamic measurements in fully awake animals. Bladder function of female Lewis rats was investigated in naïve animals by metabolic cage at baseline, 14-16 days after bladder catheter and external urethral sphincter electromyography electrode implantation in fully awake animals by urodynamics, and again by metabolic cage. Investigating the same animals (n = 8), voided volume, average flow, and duration of voiding were similar (P > 0.05) in naïve animals measured by metabolic cage and after catheter implantation by urodynamic measurements and by metabolic cage. In naïve animals measured by metabolic cage, voided volumes were significantly different in the light (resting phase) versus the dark (active phase) part of the 24 h cycle (mean difference 0.14 mL, 21%, P = 0.004, n = 27). Lower urinary tract function assessed by metabolic cage or by urodynamic meaurements in fully awake rats was indistinguishable. Thus, catheter implantation did not significantly change physiological bladder function. This shows that urodynamic measurements in awake animals are an appropriate approach to study lower urinary tract function in health and disease in animal models, directly paralleling the human diagnostic procedures. © 2017 Wiley Periodicals, Inc.

Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats: Effects on Brain and Behavior

DTIC Science & Technology

2015-03-01

Analysis of seizure activity and dendritic spine density following exposure to sarin during puberty Methods Female rats were surgically implanted...effects were observed in rats exposed to GB on PND 7 or 21. This study shows that nerve agent exposure during puberty results in severe and life

Biocompatibility evaluation of 3 facial silicone elastomers.

PubMed

França, Diurianne Caroline Campos; de Castro, Alvimar Lima; Soubhia, Ana Maria Pires; Tucci, Renata; de Aguiar, Sandra Maria Herondina Coelho Ávila; Goiato, Marcelo Coelho

2011-05-01

The failure of facial prostheses is caused by limitations in the properties of existing materials, especially the biocompatibility. This study aimed to evaluate the biocompatibility of maxillofacial silicones in subcutaneous tissue of rats. Thirty Wistar rats received subcutaneous implants of 3 maxillofacial silicone elastomers (LIM 6050, MDX 4-4210, and industrial Silastic 732 RTV). A histomorphometric evaluation was conducted to analyze the biocompatibility of the implants. Eight areas of 60.11 mm(2) from the surgical pieces were analyzed. Mesenchymal cells, eosinophils, and foreign-body giant cells were counted. Data were submitted to analysis of variance and Tukey test. Initially, all implanted materials exhibited an acceptable tissue inflammatory response, with tissue reactions varying from light to moderate. Afterward, a fibrous capsule around the silicone was observed. The silicones used in the current study presented biocompatibility and can be used for implantation in both medical and dental areas. Their prosthetic indication is conditioned to their physical properties. Solid silicone is easier to adapt and does not suffer apparent modifications inside the tissues.

Enhanced healing of rat calvarial critical size defect with selenium-doped lamellar biocomposites.

PubMed

Wang, Yanhua; Lv, Peng; Ma, Zhe; Zhang, Jingcheng

2013-10-01

A 3D porous lamellar selenium-containing nano-hydroxyapatite (SeHAN)/chitosan (CS) biocomposite was synthesized. The selenium-containing hydroxyapatite (HA) grains of 150~200 nm in length and 20~30 nm in width were observed by dynamic light scattering and transmission electron microscopy. A combination of X-ray diffraction, Fourier-transform infrared spectroscopy, and SEM indicated that HA particles were uniformly dispersed in chitosan matrix and there was a chemical interaction between chitosan and HA. Then, a standard critical size calvarial bone defect was created in Wistar rats. In group 1, no implant was made in the defect. In groups 2 and 3, HA nanoparticles (HAN)/CS biocomposite and SeHAN/CS biocomposite were implanted into the defect, respectively. After 4 weeks, the histological assessment clearly exhibited no significant changes, only found some living cells anchored in the periphery of the implants. After 8 and 12 weeks, most newly formed osteoid tissue was found in the SeHAN/CS implant group. Additionally, the newly formed osteoid tissue, both at the edge and in the center of implants, was bioactive and neovascularized. Microfocus computerized tomography measurements also confirmed the much better quality of the newly formed bone tissue in SeHAN/CS implant group than that in HAN/CS implant group (p < 0.01). Collectively, the SeHAN/CS biocomposite, as a bioactive bone grafting substitute, significantly enhanced the repair of bone defect.

Simple 3,4-Dihydroxy-L-Phenylalanine Surface Modification Enhances Titanium Implant Osseointegration in Ovariectomized Rats.

PubMed

Ma, Ting; Ge, Xi-Yuan; Hao, Ke-Yi; Zhang, Bi-Ru; Jiang, Xi; Lin, Ye; Zhang, Yu

2017-12-19

Osteoporosis presents a challenge to the long-term success of osseointegration of endosseous implants. The bio-inspired 3,4-dihydroxy-L-phenylalanine (Dopa) coating is widely used as a basic layer to bind osteogenetic molecules that may improve osseointegration. To date, little attention has focused on application of Dopa alone or binding inhibitors of bone resorption in osteoporosis. Local use of a bisphosphonate such as zoledronic acid (ZA), an inhibitor of osteoclast-mediated bone resorption, has been proven to improve implant osseointegration. In this study, ovariectomized rats were divided into four groups and implanted with implants with different surface modifications: sandblasted and acid-etched (SLA), SLA modified with Dopa (SLA-Dopa), SLA modified with ZA (SLA-ZA), and SLA modified with Dopa and ZA (SLA-Dopa + ZA). Measurement of removal torque, micro-computed tomography and histology revealed a greater extent of bone formation around the three surface-modified implants than SLA-controls. No synergistic effect was observed for combined Dopa + ZA coating. Microarray analysis showed the Dopa coating inhibited expression of genes associated with osteoclast differentiation, similarly to the mechanism of action of ZA. Simple Dopa modification resulted in a similar improvement in osseointegration compared to ZA. Thus, our data suggest simple Dopa coating is promising strategy to promote osseointegration of implants in patients with osteoporosis.

Long-term Calibration Considerations during Subcutaneous Microdialysis Sampling in Mobile Rats

PubMed Central

Mou, Xiaodun; Lennartz, Michelle; Loegering, Daniel J.; Stenken, Julie A.

2010-01-01

The level at which implanted sensors and sampling devices maintain their calibration is an important research area. In this work, microdialysis probes with identical geometry and different membranes, polycarbonate/polyether (PC) or polyethersulfone (PES), were used with internal standards (vitamin B12 (MW 1355), antipyrine (MW 188) and 2-deoxyglucose (2-DG, MW 164)) and endogenous glucose to investigate changes in their long-term calibration after implantation into the subcutaneous space of Sprague-Dawley rats. Histological analysis confirmed an inflammatory response to the microdialysis probes and the presence of a collagen capsule. The membrane extraction efficiency (percentage delivered to the tissue space) for antipyrine and 2-DG was not altered throughout the implant lifetime for either PC- or PES-membranes. Yet, Vitamin B12 extraction efficiency and collected glucose concentrations decreased during the implant lifetime. Antipyrine was administered i.v. and its concentrations obtained in both PC-and PES-membrane probes were significantly reduced between the implant day and seven (PC) or 10 (PES) days post implantation suggesting that solute supply is critical for in vivo extraction efficiency. For the low molecular weight solutes such as antipyrine and glucose, localized delivery is not affected by the foreign body reaction, but recovery is significantly reduced. For Vitamin B12, a larger solute, the fibrotic capsule formed around the probe significantly restricts diffusion from the implanted microdialysis probes. PMID:20223515

Evaluation of subcutaneous and alveolar implantation surgical sites in the study of the biological properties of root-end filling endodontic materials

PubMed Central

CINTRA, Luciano Tavares Angelo; BERNABÉ, Pedro Felício Estrada; de MORAES, Ivaldo Gomes; GOMES-FILHO, João Eduardo; OKAMOTO, Tetuo; CONSOLARO, Alberto; PINHEIRO, Tiago Novaes

2010-01-01

Objective The aim of this study was to compare two methodologies used in the evaluation of tissue response to root-end filling materials in rats. Material and Methods Forty rats were divided into 4 groups: in Groups I and II (control groups), empty polyethylene tubes were implanted in the extraction site and in the subcutaneous tissue, respectively; in Groups III and IV, polyethylene tubes filled with ProRoot MTA were implanted in the extraction site and in the subcutaneous tissue, respectively. The animals were killed 7 and 30 days after tube implantation, and the hemi-maxillas and the capsular subcutaneous tissue, both with the tubes, were removed. Specimens were processed and evaluated histomorphologicaly under light microscopy. The scores obtained were analyzed statistically by the Kruskal-Wallis test (p<0.05). Results There were no statistically significant differences between the implantation methods (p=0.78033, p=0.72039). It was observed that the 30-day groups presented a more mature healing process due to smaller number of inflammatory cells. Conclusion The present study showed no differences in tissue responses as far as the implantation site and the studied period were concerned. Alveolar socket implantation methodology represents an interesting method in the study of the biological properties of root-end filling endodontic materials due to the opportunity to evaluate bone tissue response. PMID:20379685

Histopathological reaction over prosthesis surface covered with silicone and polyurethane foam implanted in rats.

PubMed

Wagenführ-Júnior, Jorge; Ribas Filho, Jurandir Marcondes; Nascimento, Marcelo Mazza do; Ribas, Fernanda Marcondes; Wanka, Marcus Vinícius; Godoi, Andressa de Lima

2012-12-01

To evaluate whether polyurethane foam leads more intense foreign-body reaction than silicone foam. To compare the vascularization of the capsules surrounding the foam implants. To investigate if the capsule of polyurethane foam implanted has greater amount of collagen than that of silicone foam. Sixty-four young male Wistar rats were allocated into two groups: polyurethane foam and silicone foam. Subcutaneous discs were implanted into the dorsum of the animals in both groups. The capsules were assessed 28 days, two months, three months and six months postoperatively. Microscopic analysis with H&E stain was performed to evaluate the acute and chronic inflammatory process, foreign-body reaction and neovascularization. The analysis with picrosirius red was performed using the ImageProPlus software, to measure the number of vessels and collagen types I and III. There were no statistical differences between the two groups regarding the acute and chronic inflammatory processes. All rats from the polyurethane group, in all times, exhibited moderate or intense foreign-body reaction, with statistic significant difference (p=0.046) when compared with the silicone group, in which the reaction was either mild or nonexistent at two months. Vascular proliferation was significantly different between the groups at 28 days (p=0.0002), with the polyurethane group displaying greater neovascularization with H&E stain. Similar results were obtained with picrosirius red, which revealed in the polyurethane group a much greater number of vessels than in the silicone group (p=0.001). The collagen area was larger in the polyurethane group, significantly at 28 days (p=0.001) and at two months (p=0.030). Polyurethane foam elicited more intense foreign-body reaction when compared with silicone foam. The number of vessels was higher in the capsules of the polyurethane foam implants 28 days after the operation. The capsule of the polyurethane foam implants showed a greater amount of collagen than that of the silicone foam implants.

[Experimental study of the effect of new bone formation on new type artificial bone composed of bioactive ceramics].

PubMed

Zhu, Minghua; Zeng, Yi; Sun, Tao; Peng, Qiang

2005-03-15

To investigate the osteogenic potential of four kinds of new bioactive ceramics combined with bovine bone morphogenetic proteins (BMP) and to explore the feasibility of using compounds as bone substitute material. Ninety-six rats were divided into 4 groups (24 in each group). BMP was combined with hydroxyapatite (HA), tricalcium phosphate (TCP), fluoridated-HA (FHA), and collagen-HA(CHA) respectively. The left thighs of the rats implanted with HA/BMP, TCP/BMP, FHA/BMP, and CHA/BMP were used as experimental groups. The right thighs of the rats implanted with HA, TCP, CHA, and decalcified dentin matrix (DDM) were used as control groups. The rats were sacrificed 1, 3, 5 and 7 weeks after implantation and bone induction was estimated by alkaline phosphatase (ALP), phosphorus (P), and total protein (TP) measurement. The histological observation and electronic microscope scanning of the implants were also made. The cartilage growth in the 4 experimental groups and the control group implanted with DDM was observed 1 week after operation and fibrous connective tissues were observed in the other 3 control groups. 3 weeks after implantation, lamellar bone with bone marrow and positive reaction in ALP stain were observed in the 4 experimental groups. No bone formation or positive reaction in ALP stain were observed in the control groups. The amount of ALP activity, P value, and new bone formation in the experimental groups were higher than those in the control group(P < 0.05). The amount of ALP activity, P value, and new bone formation in TCP/BMP group were higher than those in HA/BMP, CHA/BMP and FHA/BMP groups (P < 0.05). There was no significant difference in TP between the BMP treatment group and the control groups. From 5th to 7th week, new bone formation, histochemistry evaluation, and the level of ALP, P, TP value were as high as those in the 3rd week. New composite artificial bone of TCP/BMP, HA/BMP, CHA/BMP, and FHA/BMP all prove to be effective, but TCP/BMP is the most effective so that it is the most suitable biomaterial replacement of tissue.

Implanted neural progenitor cells regulate glial reaction to brain injury and establish gap junctions with host glial cells.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Macías, David; Gálvez, Victoria; Pastor, Angel M

2014-04-01

Transplantation of neural stem/progenitor cells (NPCs) in the lesioned brain is able to restore morphological and physiological alterations induced by different injuries. The local microenvironment created at the site of grafting and the communication between grafted and host cells are crucial in the beneficial effects attributed to the NPC implants. We have previously described that NPC transplantation in an animal model of central axotomy restores firing properties and synaptic coverage of lesioned neurons and modulates their trophic factor content. In this study, we aim to explore anatomical relationships between implanted NPCs and host glia that might account for the implant-induced neuroprotective effects. Postnatal rat subventricular zone NPCs were isolated and grafted in adult rats after transection of the medial longitudinal fascicle. Brains were removed and analyzed eight weeks later. Immunohistochemistry for different glial markers revealed that NPC-grafted animals displayed significantly greater microglial activation than animals that received only vehicle injections. Implanted NPCs were located in close apposition to activated microglia and reactive astrocytes. The gap junction protein connexin43 was present in NPCs and glial cells at the lesion site and was often found interposed within adjacent implanted and glial cells. Gap junctions were identified between implanted NPCs and host astrocytes and less frequently between NPCs and microglia. Our results show that implanted NPCs modulate the glial reaction to lesion and establish the possibility of communication through gap junctions between grafted and host glial cells which might be involved in the restorative effects of NPC implants. Copyright © 2014 Wiley Periodicals, Inc.

Analgesia Induced by Isolated Bovine Chromaffin Cells Implanted in Rat Spinal Cord

NASA Astrophysics Data System (ADS)

Sagen, Jacqueline; Pappas, George D.; Pollard, Harvey B.

1986-10-01

Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffin cells were implanted into the subarachnoid space of the lumbar spinal region in adult rats. Pain sensitivity and response to nicotine stimulation was determined at various intervals following cell implantation. Low doses of nicotine were able to induce potent analgesia in implanted animals as early as one day following their introduction into the host spinal cord. This response could be elicited at least through the 4 months the animals were tested. The induction of analgesia by nicotine in implanted animals was dose related. This analgesia was blocked by the opiate antagonist naloxone and partially attenuated by the adrenergic antagonist phentolamine. These results suggest that the analgesia is due to the stimulated release of opioid peptides and catecholamines from the implanted bovine chromaffin cells and may provide a new therapeutic approach for the relief of pain.

Phelligridin D-loaded oral nanotube titanium implant enhances osseointegration and prevents osteolysis in rat mandible.

PubMed

Kim, Ji-Eun; Takanche, Jyoti Shrestha; Kim, Jeong-Seok; Lee, Min-Ho; Jeon, Jae-Gyu; Park, Il-Song; Yi, Ho-Keun

2018-04-12

Poor bone quality and osteolysis are the major causes of implant failure in dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes titanium (Ti) for bone formation around the dental implants. The purpose of this study was to enhance osseointegration of phelligridin D-loaded implant into the bone for bone formation and prevention of osteolysis. Cell viability, crystal violet staining, Western blot, alizarin red S staining, alkaline phosphatase activity, tartrate-resistant acid phosphatase staining, micro-computed tromography (μ-CT), hematoxylin and eosin (H&E) and immunohistochemical staining were used in vitro and in vivo to test the biocompatibility of phelligridin D. Phelligridin D enhanced osteoblast differentiation and mineralization by increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2, osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast differentiation by decreasing receptor activator of nuclear factor kappa-B ligand (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in a rat model. Phelligridin D also inhibited osteolysis by suppressing the expression of RANKL. These findings strongly suggest that phelligridin D is a new compound representing a potential therapeutic candidate for implant failure caused by osteolysis and poor bone quality of teeth.

Histological evaluation of capsules formed by silicon implants coated with polyurethane foam and with a textured surface in rats.

PubMed

Silva, Eduardo Nascimento; Ribas-Filho, Jurandir Marcondes; Czeczko, Nicolau Gregori; Pachnicki, Jan Pawel Andrade; Netto, Mário Rodrigues Montemor; Lipinski, Leandro Cavalcante; Noronha, Lucia de; Colman, Joelmir; Zeni, João Otavio; Carvalho, Caroline Aragão de

2016-12-01

To assess the capsules formed by silicone implants coated with polyurethane foam and with a textured surface. Sixty-four Wistar albinus rats were divided into two groups of 32 each using polyurethane foam and textured surface. The capsules around the implants were analyzed for 30, 50, 70 and 90 days. Were analyzed the following parameters: foreign body reaction, granulation tissue, presence of myofibroblasts, neoangiogenesis, presence of synovial metaplasia, capsular thickness, total area and collagen percentage of type I and III, in capsules formed around silicone implants in both groups. The foreign body reaction was only present in the four polyurethane subgroups. The formation of granulation tissue and the presence of myofibroblasts were higher in the four polyurethane subgroups. Regarding to neoangiogenesis and synovial metaplasia, there was no statistical difference between the groups. Polyurethane group presented (all subgroups) a greater capsule thickness, a smaller total area and collagen percentage of type I and a higher percentage area of type III, with statistical difference. The use of polyurethane-coated implants should be stimulated by the long-term results in a more stable capsule and a lower incidence of capsular contracture, despite developing a more intense and delayed inflammatory reaction in relation to implants with textured surface.

Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

PubMed

McNicholas, Colleen; Swor, Erin; Wan, Leping; Peipert, Jeffrey F

2017-06-01

The subdermal contraceptive implant and the 52-mg levonorgestrel intrauterine device are currently Food and Drug Administration approved for 3 and 5 years of use, respectively. Limited available data suggested both of these methods are effective beyond that time. Demonstration of prolonged effectiveness will improve the cost-effectiveness of the device, and potentially patient continuation and satisfaction. We sought to evaluate the effectiveness of the contraceptive implant and the 52-mg hormonal intrauterine device in women using the method for 2 years beyond the current Food and Drug Administration-approved duration. We initiated this ongoing prospective cohort study in January 2012. We are enrolling women using the contraceptive implant or 52-mg levonorgestrel intrauterine device for a minimum of 3 and 5 years, respectively (started intrauterine device in ≥2007 or implant in ≥2009). Demographic and reproductive health histories, as well as objective body mass index, were collected. Implant users were offered periodic venipuncture for analysis of serum etonogestrel levels. The primary outcome, unintended pregnancy rate, was calculated per 100 woman-years. We analyzed baseline demographic characteristics using χ 2 test and Fisher exact test, and compared serum etonogestrel levels stratified by body mass index using the Kruskal-Wallis test. Implant users (n = 291) have contributed 444.0 woman-years of follow-up. There have been no documented pregnancies in implant users during the 2 years of postexpiration follow-up. Calculated failure rates in the fourth and fifth years for the implant are calculated as 0 (1-sided 97.5% confidence interval, 0-1.48) per 100 woman-years at 4 years and 0 (1-sided 97.5% confidence interval, 0-2.65) per 100 woman-years at 5 years. Among 496 levonorgestrel intrauterine device users, 696.9 woman-years of follow-up have been completed. Two pregnancies have been reported. The failure rate in the sixth year of use of the levonorgestrel intrauterine device is calculated as 0.25 (95% confidence interval, 0.04-1.42) per 100 woman-years; failure rate during the seventh year is 0.43 (95% confidence interval, 0.08-2.39) per 100 woman-years. Among implant users with serum etonogestrel results, the median etonogestrel level was 207.7 pg/mL (range 63.8-802.6 pg/mL) at the time of method expiration, 166.1 pg/mL (range 67.9 25.0-470.5 pg/mL) at the end of the fourth year, and 153.0 pg/mL (range 72.1-538.8 pg/mL) at the end of the fifth year. Median etonogestrel levels were compared by body mass index at each time point and a statistical difference was noted at the end of 4 years of use with overweight women having the highest serum etonogestrel (195.9; range 25.0-450.5 pg/mL) when compared to normal (178.9; range 87.0-463.7 pg/mL) and obese (137.9; range 66.0-470.5 pg/mL) women (P = .04). This study indicates that the contraceptive implant and 52-mg hormonal intrauterine device continue to be highly effective for at least 2 additional years of use. Serum etonogestrel evaluation demonstrates median levels remain above the ovulation threshold of 90 pg/mL for women in all body mass index classes. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of therapeutic ultrasound on metallic implants: a study in rats.

PubMed

Kocaoğlu, Barış; Cabukoglu, Cengiz; Ozeras, Nadire; Seyhan, Mustafa; Karahan, Mustafa; Yalcin, Selim

2011-11-01

To investigate whether therapeutic ultrasound (US) use over metallic implants has the potential for adverse effects as a result of greater temperature increases at the tissue-metal interface. A randomized controlled trial. A research laboratory. Sprague-Dawley rats (N=40; weight, 230-300g) were used and divided into 3 study groups. In group 1, both limbs of 10 rats were used for evaluation of temperature changes. Metal pins were placed into the femur of the left limb, and the right limbs were used as controls. A thermal sensor was placed into the medulla to record the elevation of tissue temperature during US application. In groups 2 and 3 with 15 rats in each, a midshaft femoral fracture was produced, and intramedullary fixation was performed with metal pins. Group 2 received US treatment for 5 minutes daily and continued for 27 days. Group 3 served as controls. The rats in groups 2 and 3 were killed on postoperative day 30. The specimens were evaluated by radiology, histopathology, and biomechanics. The presence of metal in bone did not cause an increased temperature rise. US application did not increase or decrease callus formation, and there was no tissue necrosis. The average removal torques of pins in groups did not show a significant difference. Internal fixation with metallic implants may not be a contraindication for therapeutic US treatment. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of metal concentrations in rat tibia tissues with various metallic implants.

PubMed

Okazaki, Yoshimitsu; Gotoh, Emiko; Manabe, Takeshi; Kobayashi, Kihei

2004-12-01

To compare metal concentrations in tibia tissues with various metallic implants, SUS316L stainless steel, Co-Cr-Mo casting alloy, and Ti-6Al-4V and V-free Ti-15Zr-4Nb-4Ta alloys were implanted into the rat tibia for up to 48 weeks. After the implant was removed from the tibia by decalcification, the tibia tissues near the implant were lyophilized. Then the concentrations of metals in the tibia tissues by microwave acid digestion were determined by inductively coupled plasma-mass spectrometry. Fe concentrations were determined by graphite-furnace atomic absorption spectrometry. The Fe concentration in the tibia tissues with the SUS316L implant was relatively high, and it rapidly increased up to 12 weeks and then decreased thereafter. On the other hand, the Co concentration in the tibia tissues with the Co-Cr-Mo implant was lower, and it increased up to 24 weeks and slightly decreased at 48 weeks. The Ni concentration in the tibia tissues with the SUS316L implant increased up to 6 weeks and then gradually decreased thereafter. The Cr concentration tended to be higher than the Co concentration. This Cr concentration linearly increased up to 12 weeks and then decreased toward 48 weeks in the tibia tissues with the SUS316L or Co-Cr-Mo implant. Minute quantities of Ti, Al and V in the tibia tissues with the Ti-6Al-4V implant were found. The Ti concentration in the tibia tissues with the Ti-15Zr-4Nb-4Ta implant was lower than that in the tibia tissues with the Ti-6Al-4V implant. The Zr, Nb and Ta concentrations were also very low. The Ti-15Zr-4Nb-4Ta alloy with its low metal release in vivo is considered advantageous for long-term implants.

Correlation between rate of bony ingrowth to stainless steel, pure titanium, and titanium alloy implants in vivo and formation of hydroxyapatite on their surfaces in vitro.

PubMed

Oron, A; Agar, G; Oron, U; Stein, A

2009-12-15

The rate of bony ingrowth to identical metal implants made of either pure titanium (cpTi), titanium alloy (Ti-6Al-4V), or stainless steel 316L (SS) inserted to the medullar canal of the femur in rats was investigated. The kinetics of spontaneous deposition of hydroxyapatite (HA) globules on the aforementioned metals in vitro during incubation in simulated body fluid (SBF) was also studied. It was found that the rate of increased bonding strength between the cpTi implants and the host bone was the highest, whereas around the SS implants it was the slowest. At 10 days postimplant insertion, the shear strength of the cpTi implants was 2.2- and 4-fold significantly higher than for the Ti-6Al-4V and the SS implants, respectively. Spontaneous formation of the HA globules on the cpTi and Ti-6Al-4V implants that were incubated in the SBF was observed as early as 6 and 10 days after incubation in SBF, respectively, whereas on SS implants, deposition of HA was evident only after 2 weeks of in vitro incubation in SBF. It is concluded that the chemical surface characteristics and the biocompatibility of the implants probably play a key role in the process of bone growth next to them, during the formation of bone in vivo. The rate of bony ingrowth to various metal implants alloys inserted into the medullar canal of rats correlates well with the induction of apatite formation on them during incubation in vitro with SBF.

In vivo performance of an acellular disc-like angle ply structure (DAPS) for total disc replacement in a small animal model.

PubMed

Martin, John T; Kim, Dong Hwa; Milby, Andrew H; Pfeifer, Christian G; Smith, Lachlan J; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2017-01-01

Total intervertebral disc replacement with a biologic engineered disc may be an alternative to spinal fusion for treating end-stage disc disease. In previous work, we developed disc-like angle ply structures (DAPS) that replicate the structure and function of the native disc and a rat tail model to evaluate DAPS in vivo. Here, we evaluated a strategy in which, after in vivo implantation, endogenous cells could colonize the acellular DAPS and form an extracellular matrix organized by the DAPS topographical template. To do so, acellular DAPS were implanted into the caudal spines of rats and evaluated over 12 weeks by mechanical testing, histology, and microcomputed tomography. An external fixation device was used to stabilize the implant site and various control groups were included to evaluate the effect of immobilization. There was robust tissue formation within the DAPS after implantation and compressive mechanical properties of the implant matched that of the native motion segment. Immobilization provided a stable site for fibrous tissue formation after either a discectomy or a DAPS implantation, but bony fusion eventually resulted, with segments showing intervertebral bridging after long-term implantation, a process that was accelerated by the implanted DAPS. Thus, while compressive mechanical properties were replicated after DAPS implantation, methods to actively prevent fusion must be developed. Future work will focus on limiting fusion by remobilizing the motion segment after a period of integration, delivering pro-chondrogenic factors, and pre-seeding DAPS with cells prior to implantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:23-31, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A biological study establishing the endotoxin limit of biomaterials for bone regeneration in cranial and femoral implantation of rats.

PubMed

Haishima, Yuji; Hasegawa, Chie; Todoki, Kazuo; Sasaki, Kazuo; Niimi, Shingo; Ozono, Satoru

2017-08-01

The purpose of this study was to accurately quantify the risk of endotoxin contamination in biomaterials for bone regeneration in order to establish the acceptable endotoxin limit. Collagen sheets containing varying amounts of purified endotoxin from Escherichia coli and dried, heat-killed E. coli or Staphylococcus aureus cells were implanted into cranial or femoral defects in rats. These defects were artificially prepared to a size of 5 × 5 mm or a diameter of 1 mm, respectively. The degree of osteoanagenesis was assessed by soft X-ray radiography and histopathology at 1 and 4 weeks after implantation. The collagen sheet containing the dried E. coli cells showed a dose-dependent delay in cranial and/or femoral osteoanagenesis at endotoxin activities of more than 33.6 EU/mg, at which no inflammatory response was observed. In contrast, no such observation occurred with the collagen sheet containing S. aureus cells. These results suggest that endotoxins may affect the process of osteoanagenesis. Additionally, the no-observed-adverse-effect level was 9.6 EU/mg, corresponding to 255 EU/kg body weight in rats. Interestingly, no delay in osteoanagenesis was induced by the implantation of collagen sheets containing purified endotoxin at any dose tested. This suggested that pure endotoxin implanted into tissues having poor circulation of bodily fluids without bleeding may not be recognized as a foreign substance and may not induce a significant biological response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1514-1524, 2017. © 2016 Wiley Periodicals, Inc.

Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

PubMed

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

2016-01-01

Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

A Novel Telometric Metric for In-Situ Measurement of Intrauterine Pressure (IUP) in Pregnant and Parturient Rats

NASA Technical Reports Server (NTRS)

Baer, Lisa A.; LaFramboise, M. N.; Hills, E. M.; Daly, M. E.; Mills, N. A.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

2001-01-01

During labor and birth, considerable forces exerted on fetuses help instigate certain adaptive postpartum responses (viz., breathing and suckling). To make precise, reliable measures of the forces experienced by rat fetuses during parturition, we developed a novel method for measuring intrauterine pressure (IUP) in late pregnant rats. A small (1.25 x 4cm) telemetric blood pressure sensor is fitted within a fluid-filled balloon, similar in size to a full term rat fetus. The balloon is surgically implanted in the uterus on Gestational Day 19 of the rats' 22-day pregnancy. During birth, dams are able to deliver their pups and the balloon. IUP arsenals are recorded during labor (G22 or 23) and birth. Data derived from a group of implanted rats indicated that pressures on the balloon increased across the period of birth, reaching 18 mmHg during labor, 25 mmHg during pup births and 39 mmHg just prior to delivery of the balloon. These data are within the range reported for conventional IUP measurement techniques. Dams are simultaneously videotaped, enabling us to analyze behavioral expressions of labor contractions and to integrate in-situ and behavioral findings.

L-glutamate microinjection in the preoptic area increases brain and body temperature in freely moving rats.

PubMed

Sengupta, Trina; Jaryal, Ashok K; Kumar, Velayudhan M; Mallick, Hruda N

2014-01-08

The role of the preoptic area (POA) in thermoregulation is well documented. Microinjection of various neurotransmitters into the POA in rats has been shown to influence body temperature. Alhough there are reports showing changes in temperature on administration of L-glutamate into the POA, the role of this excitatory amino acid in thermoregulation has not been studied in unanaesthetized rats. In the present study, brain and body temperatures were recorded in freely moving adult male Wistar rats with K-type thermocouple implanted near the hypothalamus and temperature transmitter implanted inside the peritoneum. Recordings were performed 2 h preinjection and 4 h postinjection. L-glutamate (0.14 nM) microinjection into the POA induced long-lasting hyperthermia and reduced locomotor activity. The rats remained curled up and showed piloerection. L-glutamate-induced hyperthermia was attenuated by previous injection of the ionotropic L-glutamate receptor antagonist, kynurenate (0.11 nM). We propose that L-glutamate in the POA participates not only in heat production and conservation but also plays a role in interlinking sleep and thermoregulation.

The effects of local nitroglycerin on the surgical delay procedure in prefabricated flaps by vascular implant in rats.

PubMed

Sá, Jairo Zacchê de; Aguiar, José Lamartine de Andrade; Cruz, Adriana Ferreira; Schuler, Alexandre Ricardo Pereira; Lima, José Ricardo Alves de; Marques, Olga Martins

2012-12-01

To evaluate the effect of local nitroglycerin on the viable area of a prefabricated flap for vascular implant in rats, and to investigate the surgical delay procedure. A femoral pedicle was implanted under the skin of the abdominal wall in forty Wistar rats. The animals were divided into four groups of ten: group 1 - without surgical delay procedure and local nitroglycerin; group 2 - with surgical delay procedure, but without local nitroglycerin; group 3 - without surgical delay procedure, but with local nitroglycerin; and group 4 - with simultaneous surgical delay procedure and local nitroglycerin. The percentages of the viable areas, in relation to the total flap, were calculated using AutoCAD R 14. The mean percentage value of the viable area was 8.9% in the group 1. 49.4% in the group 2; 8.4% in the group 3 and 1.1% in the group 4. There was significant difference between groups 1 and 2 (p=0.005), 1 and 4 (p=0.024), 2 and 3 (p=0.003), 2 and 4 (p=0.001). These results support the hypothesis that the closure of the arterial venous channels is responsible for the phenomenon of surgical delay procedure. Local nitroglycerin did not cause an increase in the prefabricated viable flap area by vascular implantation and decreased the viable flap area that underwent delay procedures.

Acute and Subacute Toxicity In Vivo of Thermal-Sprayed Silver Containing Hydroxyapatite Coating in Rat Tibia

PubMed Central

Tsukamoto, Masatsugu; Miyamoto, Hiroshi; Ando, Yoshiki; Eto, Shuichi; Akiyama, Takayuki; Yonekura, Yutaka; Mawatari, Masaaki

2014-01-01

To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment) and subacute phase (4–12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation. PMID:24779019

Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells.

PubMed

Frerichs, Onno; Fansa, Hisham; Schicht, Christoph; Wolf, Gerald; Schneider, Wolfgang; Keilhoff, Gerburg

2002-01-01

The bridging of nerve gaps is still one of the major problems in peripheral nerve surgery. The present experiment describes our attempt to engineer different biologic nerve grafts in a rat sciatic nerve model: cultured isogenic Schwann cells were implanted into 2-cm autologous acellular nerve grafts or autologous predegenerated nerve grafts. Autologous nerve grafts and predegenerated or acellular nerve grafts without implanted Schwann cells served as controls. The regenerated nerves were assessed histologically and morphometrically after 6 weeks. Predegenerated grafts showed results superior in regard to axon count and histologic appearance in comparison to standard grafts and acellular grafts. The acellular nerve grafts showed the worst histologic picture, but axon counts were in the range of standard grafts. The implantation of Schwann cells did not yield significant improvements in any group. In conclusion, the status of activation of Schwann cells and the stadium of Wallerian degeneration in a nerve graft might be key factors for regeneration, rather than total number of Schwann cells. Predegenerated nerve grafts are therefore superior to standard grafts in the rat model. Acellular grafts are able to bridge nerve gaps of up to 2 cm in the rat model, but even the addition of cultivated Schwann cells did not lead to results as good as in the group with autologous nerve grafts. Copyright 2002 Wiley-Liss, Inc. MICROSURGERY 22:311-315 2002

Electrophoretic deposition of ligand-free platinum nanoparticles on neural electrodes affects their impedance in vitro and in vivo with no negative effect on reactive gliosis.

PubMed

Angelov, Svilen D; Koenen, Sven; Jakobi, Jurij; Heissler, Hans E; Alam, Mesbah; Schwabe, Kerstin; Barcikowski, Stephan; Krauss, Joachim K

2016-01-12

Electrodes for neural stimulation and recording are used for the treatment of neurological disorders. Their features critically depend on impedance and interaction with brain tissue. The effect of surface modification on electrode impedance was examined in vitro and in vivo after intracranial implantation in rats. Electrodes coated by electrophoretic deposition with platinum nanoparticles (NP; <10 and 50 nm) as well as uncoated references were implanted into the rat's subthalamic nucleus. After postoperative recovery, rats were electrostimulated for 3 weeks. Impedance was measured before implantation, after recovery and then weekly during stimulation. Finally, local field potential was recorded and tissue-to-implant reaction was immunohistochemically studied. Coating with NP significantly increased electrode's impedance in vitro. Postoperatively, the impedance of all electrodes was temporarily further increased. This effect was lowest for the electrodes coated with particles <10 nm, which also showed the most stable impedance dynamics during stimulation for 3 weeks and the lowest total power of local field potential during neuronal activity recording. Histological analysis revealed that NP-coating did not affect glial reactions or neural cell-count. Coating with NP <10 nm may improve electrode's impedance stability without affecting biocompatibility. Increased impedance after NP-coating may improve neural recording due to better signal-to-noise ratio.

Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory

PubMed Central

Chompre, Gladys; Cruz, Emmanuel; Maldonado, Lucianette; Rivera-Amill, Vanessa; Porter, James T.; Noel, Richard J.

2012-01-01

Despite the widespread use of antiretroviral therapy that effectively limits viral replication, memory impairment remains a dilemma for HIV infected people. In the CNS, HIV infection of astrocytes leads to the production of the HIV-1 Nef protein without viral replication. Post mortem studies have found Nef expression in hippocampal astrocytes of people with HIV associated dementia suggesting that astrocytic Nef may contribute to HIV associated cognitive impairment even when viral replication is suppressed. To test whether astrocytic expression of Nef is sufficient to induce cognitive deficits, we examined the effect of implanting primary rat astrocytes expressing Nef into the hippocampus on spatial and recognition memory. Rats implanted unilaterally with astrocytes expressing Nef showed impaired novel location and novel object recognition in comparison with controls implanted with astrocytes expressing green fluorescent protein (GFP). This impairment was correlated with an increase in chemokine ligand 2 (CCL2) expression and the infiltration of peripheral macrophages into the hippocampus at the site of injection. Furthermore, the Nef exposed rats exhibited a bilateral loss of CA3 neurons. These results suggest that Nef protein expressed by the implanted astrocytes activates the immune system leading to neuronal damage and spatial and recognition memory deficits. Therefore, the continued expression of Nef by astrocytes in the absence of viral replication has the potential to contribute to HIV associated cognitive impairment. PMID:22926191

Advances in the delivery of buprenorphine for opioid dependence

PubMed Central

Rosenthal, Richard N; Goradia, Viral V

2017-01-01

Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD. PMID:28894357

Contraception and hormonal management in the perimenopause.

PubMed

Long, Margaret E; Faubion, Stephanie S; MacLaughlin, Kathy L; Pruthi, Sandhya; Casey, Petra M

2015-01-01

This literature review focuses on contraception in perimenopausal women. As women age, their fecundity decreases but does not disappear until menopause. After age 40, 75% of pregnancies are unplanned and may result in profound physical and emotional impact. Clinical evaluation must be relied on to diagnose menopause, since hormonal levels fluctuate widely. Until menopause is confirmed, some potential for pregnancy remains; at age 45, women's sterility rate is 55%. Older gravidas experience higher rates of diabetes, hypertension, and death. Many safe and effective contraceptive options are available to perimenopausal women. In addition to preventing an unplanned and higher-risk pregnancy, perimenopausal contraception may improve abnormal uterine bleeding, hot flashes, and menstrual migraines. Long-acting reversible contraceptives, including the levonorgestrel intrauterine system (LNG-IUS), the etonogestrel subdermal implant (ESI), and the copper intrauterine device (Cu-IUD), provide high efficacy without estrogen. LNG-IUS markedly decreases menorrhagia commonly seen in perimenopause. Both ESI and LNG-IUS provide endometrial protection for women using estrogen for vasomotor symptoms. Women without cardiovascular risk factors can safely use combined hormonal contraception. The CDC's Medical Eligibility Criteria for Contraceptive Use informs choices for women with comorbidities. No medical contraindications exist for levonorgestrel emergency-contraceptive pills, though obesity does decrease efficacy. In contrast, the Cu-IUD provides reliable emergency and ongoing contraception regardless of body mass index (BMI).

A systematic review of filler agents for aesthetic treatment of HIV facial lipoatrophy (FLA).

PubMed

Jagdeo, Jared; Ho, Derek; Lo, Alex; Carruthers, Alastair

2015-12-01

HIV facial lipoatrophy (FLA) is characterized by facial volume loss. HIV FLA affects the facial contours of the cheeks, temples, and orbits, and is associated with social stigma. Although new highly active antiretroviral therapy medications are associated with less severe FLA, the prevalence of HIV FLA among treated individuals exceeds 50%. The goal of our systematic review is to examine published clinical studies involving the use of filler agents for aesthetic treatment of HIV FLA and to provide evidence-based recommendations based on published efficacy and safety data. A systematic review of the published literature was performed on July 1, 2015, on filler agents for aesthetic treatment of HIV FLA. Based on published studies, poly-L-lactic acid is the only filler agent with grade of recommendation: B. Other reviewed filler agents received grade of recommendation: C or D. Poly-L-lactic acid may be best for treatment over temples and cheeks, whereas calcium hydroxylapatite, with a Food and Drug Administration indication of subdermal implantation, may be best used deeply over bone for focal enhancement. Additional long-term randomized controlled trials are necessary to elucidate the advantages and disadvantages of fillers that have different biophysical properties, in conjunction with cost-effectiveness analysis, for treatment of HIV FLA. Published by Elsevier Inc.

Advances in the delivery of buprenorphine for opioid dependence.

PubMed

Rosenthal, Richard N; Goradia, Viral V

2017-01-01

Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD.

Treatment and prevention of HIV infection with long-acting antiretrovirals.

PubMed

Benítez-Gutiérrez, Laura; Soriano, Vicente; Requena, Silvia; Arias, Ana; Barreiro, Pablo; de Mendoza, Carmen

2018-05-01

Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

Allograft en bloc vagino-utero-ovarian avascular transplant versus autograft implantation in rats.

PubMed

Salehian, Mohammad-Taghi; Salehian, Arash; Mossaffa, Nariman; Hadian, Mehrnaz; Eghtesadi-Araghi, Payam

2008-12-01

The aim of this study was to compare the results of an allograft en bloc vagino-uteroovarian avascular transplant with those of autograft implantation in rats. Thirty-four inbred adult virgin female Albino rats (age range, 10 - 12 weeks) were divided into 2 groups: the control group (autograft, n=11) and the study group (en bloc vagino-utero-ovariectomy, n=23). In the study group, the uterus and adnexa and the ovaries of the donor rat were transplanted to the recipient animal. Twenty-five to 30 days after that procedure, all rats were killed, and the samples were assessed histopathologically. No immunosuppressive drugs were used. Ten rats died during the postoperative period. In 16 rats, the transplanted system had survived completely at the conclusion of the study. In each of the study groups, complete survival of the uterus and ovaries was noted in 8 rats (34.8% in the study group and 72.8% in the control group). In all rats except 1, histopathologic examination did not reveal any signs of the classic criteria for tissue rejection reaction. The lack of revascularization, nonspecific signs of inflammation, and the presence of large granular lymphocytes and natural killer cells were reported. Our data indicated that the outcome of both allograft and homograft avascular en bloc transplant of vagino-utero-ovariectomy in rats was successful, and that immunologic rejection did not seem to have an important role in those procedures.

Characterization of interfragmentary motion associated with common osteosynthesis devices for rat fracture healing studies.

PubMed

Meyers, Nicholaus; Sukopp, Matthias; Jäger, Rudolf; Steiner, Malte; Matthys, Romano; Lapatki, Bernd; Ignatius, Anita; Claes, Lutz

2017-01-01

Rat models are widely used in preclinical studies investigating fracture healing. The interfragmentary movement at a fracture site is critical to the course of healing and therefore demands definition in order to aptly interpret the experimental results. Estimation of this movement requires knowledge of the fixation stiffness and loading. The characteristic loading for the rat femur has been estimated, but the stiffness of fixation used in rat studies has yet to be fully described. This study aimed to determine the 6 degree of freedom stiffness of four commonly used implants, two external fixators (RatExFix and UlmExFix), a locking plate, and a locking intramedullary nail, in all degrees of freedom and estimate the interfragmentary movement under specific physiological loads. The external fixator systems allow the greatest movement. Mounted 45° anterolateral on the femur, the RatExFix allows an average of 0.88 mm of motion in each anatomic direction while the stiffer UlmExFix allows about 0.6 mm of motion. The nail is far stiffer than the other implants investigated while the plate allows movement of an intermediate magnitude. Both the nail and plate demonstrate higher axial than shear stiffness. The relatively large standard deviations in external fixator shear motion imply strong dependence on bone axis alignment across the gap and the precise orientation of the specimen relative to the loading. The smaller standard deviation associated with the nail and plate results from improved alignment and minimization of the influence of rotational positioning of the specimen due to the reduced implant eccentricity relative to the specimen axis. These results show that the interfragmentary movement is complex and varies significantly between fixation devices but establishes a baseline for the evaluation of the results of different studies.

Characterization of interfragmentary motion associated with common osteosynthesis devices for rat fracture healing studies

PubMed Central

Steiner, Malte; Matthys, Romano; Lapatki, Bernd; Ignatius, Anita; Claes, Lutz

2017-01-01

Rat models are widely used in preclinical studies investigating fracture healing. The interfragmentary movement at a fracture site is critical to the course of healing and therefore demands definition in order to aptly interpret the experimental results. Estimation of this movement requires knowledge of the fixation stiffness and loading. The characteristic loading for the rat femur has been estimated, but the stiffness of fixation used in rat studies has yet to be fully described. This study aimed to determine the 6 degree of freedom stiffness of four commonly used implants, two external fixators (RatExFix and UlmExFix), a locking plate, and a locking intramedullary nail, in all degrees of freedom and estimate the interfragmentary movement under specific physiological loads. The external fixator systems allow the greatest movement. Mounted 45° anterolateral on the femur, the RatExFix allows an average of 0.88 mm of motion in each anatomic direction while the stiffer UlmExFix allows about 0.6 mm of motion. The nail is far stiffer than the other implants investigated while the plate allows movement of an intermediate magnitude. Both the nail and plate demonstrate higher axial than shear stiffness. The relatively large standard deviations in external fixator shear motion imply strong dependence on bone axis alignment across the gap and the precise orientation of the specimen relative to the loading. The smaller standard deviation associated with the nail and plate results from improved alignment and minimization of the influence of rotational positioning of the specimen due to the reduced implant eccentricity relative to the specimen axis. These results show that the interfragmentary movement is complex and varies significantly between fixation devices but establishes a baseline for the evaluation of the results of different studies. PMID:28453556

[Significance of various implantate localizations of Sparks prostheses, experimental studies in rats].

PubMed

Brieler, H S; Parwaresch, R; Thiede, A

1976-01-01

Our investigations show that Sparks prostheses after subcutaneous implantation are suitable for vascular grafting. At the end of the organization period the connective tissue becomes strong, and after the third and fourth weeks collagenous and elastic fibers can be seen. Ten weeks after s.c. implantation, collagenous fibers predominate. After this the Sparks prostheses can be used as a vascular graft. Intraperitoneal implantation, however, shows a histologically different picture with characteristic findings: only fat cells can be observed, a strong granulation tissue with elastic and collagenous fibers is not present. After intraperitoneal implantation Sparks prostheses are therefore unsuitable for vascular grafts.

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Pastor, Angel M

2013-01-01

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants.

Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats.

PubMed

Bussey, C T; Leeuw, A E de; Cook, R F; Ashley, Z; Schofield, J; Lamberts, R R

2014-07-01

Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 µg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the β-adrenoceptor agonist dobutamine (30 µg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The effects of implant topography on osseointegration under estrogen deficiency induced osteoporotic conditions: Histomorphometric, transcriptional and ultrastructural analysis.

PubMed

Du, Zhibin; Xiao, Yin; Hashimi, Saeed; Hamlet, Stephen M; Ivanovski, Saso

2016-09-15

Compromised bone quality and/or healing in osteoporosis are recognised risk factors for impaired dental implant osseointegration. This study examined the effects of (1) experimentally induced osteoporosis on titanium implant osseointegration and (2) the effect of modified implant surface topography on osseointegration under osteoporosis-like conditions. Machined and micro-roughened surface implants were placed into the maxillary first molar root socket of 64 ovariectomised and sham-operated Sprague-Dawley rats. Subsequent histological and SEM observations showed tissue maturation on the micro-rough surfaced implants in ovariectomised animals as early as 3days post-implantation. The degree of osseointegration was also significantly higher around the micro-rough implants in ovariectomised animals after 14days of healing although by day 28, similar levels of osseointegration were found for all test groups. The micro-rough implants significantly increased the early (day 3) gene expression of alkaline phosphatase, osteocalcin, receptor activator of nuclear factor kappa-B ligand and dentin matrix protein 1 in implant adherent cells. By day 7, the expression of inflammatory genes decreased while the expression of the osteogenic markers increased further although there were few statistically significant differences between the micro-rough and machined surfaces. Osteocyte morphology was also affected by estrogen deficiency with the size of the cells being reduced in trabecular bone. In conclusion, estrogen deficiency induced osteoporotic conditions negatively influenced the early osseointegration of machined implants while micro-rough implants compensated for these deleterious effects by enhancing osteogenic cell differentiation on the implant surface. Lower bone density, poor bone quality and osseous microstructural changes are all features characteristic of osteoporosis that may impair the osseointegration of dental implants. Using a clinically relevant trabecular bone model in the rat maxilla, we demonstrated histologically that the negative effects of surgically-induced osteoporosis on osseointegration could be ameliorated by the biomaterial's surface topography. Furthermore, gene expression analysis suggests this may be a result of enhanced osteogenic cell differentiation on the implant surface. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of estrogen and gender on cataractogenesis induced by high-LET radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henderson, M.A.; Rusek, A.; Valluri, S.

2010-02-01

Planning for long-duration manned lunar and interplanetary missions requires an understanding of radiation-induced cataractogenesis. Previously, it was demonstrated that low-linear energy transfer (LET) irradiation with 10 Gy of {sup 60}Co {gamma} rays resulted in an increased incidence of cataracts in male rats compared to female rats. This gender difference was not due to differences in estrogen, since male rats treated with the major secreted estrogen 17-{beta}-estradiol (E2) showed an identical increase compared to untreated males. We now compare the incidence and rate of progression of cataracts induced by high-LET radiation in male and female Sprague-Dawley rats. Rats received a singlemore » dose of 1 Gy of 600 MeV {sup 56}Fe ions. Lens opacification was measured at 2-4 week intervals with a slit lamp. The incidence and rate of progression of radiation-induced cataracts was significantly increased in the animals in which estrogen was available from endogenous or exogenous sources. Male rats with E2 capsules implanted had significantly higher rates of progression compared to male rats with empty capsules implanted (P = 0.025) but not compared to the intact female rats. These results contrast with data obtained after low-LET irradiation and suggest the possibility that the different types of damage caused by high- and low-LET radiation may be influenced differentially by steroid sex hormones.« less

Bioactivity of Ti-6Al-4V alloy implants treated with ibandronate after the formation of the nanotube TiO2 layer.

PubMed

Moon, So-Hee; Lee, Seung-Jae; Park, Il-Song; Lee, Min-Ho; Soh, Yun-Jo; Bae, Tae-Sung; Kim, Hyung-Seop

2012-11-01

Nanostructure surface of titanium implants treated with anodic oxidation, heat, and bisphosphonates, has been introduced to improve osseointegration of the implants. However, no information could be found about the efficiency of these approaches on Ti-6Al-4V alloy surfaces. This study examined the drug loading capacity of anodized nanotubular Ti-6Al-4V alloy surfaces in vitro as well as the bone response to surface immobilized bisphosphonates (BPs) on anodized nanotubular Ti-6Al-4V alloy surface in tibiae of rats. Ti-6Al-4V alloy titanium was divided into two groups: (1) control group (nontreated); (2) test group (anodized, heat-, and bisphosphonate-treated group). In vitro, amount of the drug released from the both groups' specimens was examined; all samples were 1 × 2 cm in size. In vivo, the 10 implants were placed inside of tibias of five rats. After 4 weeks, the bone response of the implants was evaluated using a removal torque test, and measuring bone contact and bone area. In addition, the surfaces of the extracted implants were observed by FE-SEM and EDS. In vitro, the drug loading capacity of the Ti-6Al-4V alloy surfaces was enhanced by anodizing surface modification. The values of the removal torque, bone contact, and bone area were significantly higher in the test group (p < 0.05). Furthermore, according to the EDS analysis, the amounts of Ca and P on the surface of the extracted implants were higher in the test group. Within the limits of this experiment, results of this research demonstrated that bisphosphonate-treated Ti-6Al-4V alloy implants with nanotubular surfaces have positive effects in bone-to-implant contact. Copyright © 2012 Wiley Periodicals, Inc.

Effects of different hierarchical hybrid micro/nanostructure surfaces on implant osseointegration.

PubMed

Cheng, Bingkun; Niu, Qiang; Cui, Yajun; Jiang, Wei; Zhao, Yunzhuan; Kong, Liang

2017-06-01

Hierarchical hybrid micro/nanostructure implant surfaces are considered to better mimic the hierarchical structure of bone and the nanostructures substantively influence osseointegration through managing cell behaviors. To enhance implant osseointegration for further clinical application, we evaluated the material properties and osseointegration effects of hierarchical surfaces with different nano-morphologies, using a rat model. Two representative surface fabrication methods, hydrofluoric (HF) acid etching combined with anodization (HF + AN) or magnetron sputtering (HF + MS), were selected. Sample material properties were evaluated by scanning electron microscopy, atomic force microscopy, X-ray diffraction, X-ray photoemission spectroscopy, and epoxy resin docking tensile test. Implants with different surfaces were inserted into the distal femurs of rats. After 12 weeks, osseointegration was examined by microcomputed tomography (micro-CT), histological, and biomechanical tests. Tensile testing demonstrated high bonding strength at coating/implant in the HF + MS group. Micro-CT revealed increased bone volume/total volume and significantly reduced trabecular separation in HF + MS versus other groups. Histological analysis showed significantly higher HF + MS bone-to-implant contact (74.78 ± 4.40%) versus HF + AN (65.11 ± 5.10%) and machined samples (56.03 ± 3.23%). The maximal HF + MS pull-out force increased by 33.7% versus HF + AN. These results indicated that HF + MS surfaces exhibited superior material property in terms of bonding strength and favorable implant osseointegration compared to other groups. © 2017 Wiley Periodicals, Inc.

Effects of a hybrid micro/nanorod topography-modified titanium implant on adhesion and osteogenic differentiation in rat bone marrow mesenchymal stem cells.

PubMed

Zhang, Wenjie; Li, Zihui; Huang, Qingfeng; Xu, Ling; Li, Jinhua; Jin, Yuqin; Wang, Guifang; Liu, Xuanyong; Jiang, Xinquan

2013-01-01

Various methods have been used to modify titanium implant surfaces with the aim of achieving better osseointegration. In this study, we fabricated a clustered nanorod structure on an acid-etched, microstructured titanium plate surface using hydrogen peroxide. We also evaluated biofunctionalization of the hybrid micro/nanorod topography on rat bone marrow mesenchymal stem cells. Scanning electron microscopy and x-ray diffraction were used to investigate the surface topography and phase composition of the modified titanium plate. Rat bone marrow mesenchymal stem cells were cultured and seeded on the plate. The adhesion ability of the cells was then assayed by cell counting at one, 4, and 24 hours after cell seeding, and expression of adhesion-related protein integrin β1 was detected by immunofluorescence. In addition, a polymerase chain reaction assay, alkaline phosphatase and Alizarin Red S staining assays, and osteopontin and osteocalcin immunofluorescence analyses were used to evaluate the osteogenic differentiation behavior of the cells. The hybrid micro/nanoscale texture formed on the titanium surface enhanced the initial adhesion activity of the rat bone marrow mesenchymal stem cells. Importantly, the hierarchical structure promoted osteogenic differentiation of these cells. This study suggests that a hybrid micro/nanorod topography on a titanium surface fabricated by treatment with hydrogen peroxide followed by acid etching might facilitate osseointegration of a titanium implant in vivo.

Implanting Glioblastoma Spheroids into Rat Brains and Monitoring Tumor Growth by MRI Volumetry.

PubMed

Löhr, Mario; Linsenmann, Thomas; Jawork, Anna; Kessler, Almuth F; Timmermann, Nils; Homola, György A; Ernestus, Ralf-Ingo; Hagemann, Carsten

2017-01-01

The outcome of patients suffering from glioblastoma multiforme (GBM) remains poor with a median survival of less than 15 months. To establish innovative therapeutical approaches or to analyze the effect of protein overexpression or protein knockdown by RNA interference in vivo, animal models are mandatory. Here, we describe the implantation of C6 glioma spheroids into the rats' brain and how to follow tumor growth by MRI scans. We show that C6 cells grown in Sprague-Dawley rats share several morphologic features of human glioblastoma like pleomorphic cells, areas of necrosis, vascular proliferation, and tumor cell invasion into the surrounding brain tissue. In addition, we describe a method for tumor volumetry utilizing the CISS 3D- or contrast-enhanced T1-weighted 3D sequence and freely available post-processing software.

[Experimental study on repair of the defect of the pars interarticularis in rat with bone morphogenetic protein and fibrin glue].

PubMed

Nakamura, T

1992-07-01

The possibility of repairing the defect of the pars interarticularis (pars defect) with Bone Morphogenetic Protein (BMP) and fibrin glue was studied. The pars defect established in the 5th lumbar vertebra of Wistar rat was treated with surgical implantation of a composite consisting of BMP, fibrin glue and autologous cancellous bone. At 3, 6, 9 and 12 weeks after implantation, the osteoinductive activity in the pars defect was observed histologically and compared with that of other composite implants such as BMP with fibrin glue, autologous cancellous bone alone and autologous cancellous bone with fibrin glue. Although perfect bone fusion was not obtained with any of the composites employed, a significant increase in bone formation was seen in a composite of BMP, fibrin glue and autologous cancellous bone (p less than 0.01) as compared with that seen in the others. Consequently, implantation of BMP and fibrin glue combined with some biomaterials which support osteo-induction of BMP and stabilize the pars defect might be successfully applied to repair the pars defect.

Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

PubMed

Bi, Fanggang; Shi, Zhongli; Zhou, Chenhe; Liu, An; Shen, Yue; Yan, Shigui

2015-01-01

We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering

PubMed Central

Li, Peiqi; Hashimoto, Yoshiya; Honda, Yoshitomo; Arima, Yoshiyuki; Matsumoto, Naoyuki

2015-01-01

Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS). At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment) groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption. PMID:26516841

Static Magnetic Field Effects on Impaired Peripheral Vasomotion in Conscious Rats

PubMed Central

Okano, Hideyuki; Hatano, Naoya; Tomita, Naohide; Ikada, Yoshito

2013-01-01

We investigated the SMF effects on hemodynamics in the caudal artery-ligated rat as an in vivo ischemia model using noninvasive near-infrared spectroscopy (NIRS) combined with power spectral analysis by fast Fourier transform. Male Wistar rats in the growth stage (10 weeks old) were randomly assigned into four groups: (i) intact and nonoperated cage control (n = 20); (ii) ligated alone (n = 20); (iii) ligated and implanted with a nonmagnetized rod (sham magnet; n = 22); and (vi) ligated and implanted with a magnetized rod (n = 22). After caudal artery ligation, a magnetized or unmagnetized rod (maximum magnetic flux density of 160 mT) was implanted transcortically into the middle diaphysis of the fifth caudal vertebra. During the experimental period of 7 weeks, NIRS measurements were performed in 3- , 5- , and 7-week sessions and the vasomotion amplitude and frequency were analyzed by fast Fourier transform. Exposure for 3–7 weeks to the SMF significantly contracted the increased vasomotion amplitude in the ischemic area. These results suggest that SMF may have a regulatory effect on rhythmic vasomotion in the ischemic area by smoothing the vasomotion amplitude in the early stage of the wound healing process. PMID:24454512

Recombinant proteins secreted from tissue-engineered bioartificial muscle improve cardiac dysfunction and suppress cardiomyocyte apoptosis in rats with heart failure.

PubMed

Rong, Shu-Ling; Wang, Yong-Jin; Wang, Xiao-Lin; Lu, Yong-Xin; Wu, Yin; Liu, Qi-Yun; Mi, Shao-Hua; Xu, Yu-Lan

2010-12-01

Tissue-engineered bioartificial muscle-based gene therapy represents a promising approach for the treatment of heart diseases. Experimental and clinical studies suggest that systemic administration of insulin-like growth factor-1 (IGF-1) protein or overexpression of IGF-1 in the heart exerts a favorable effect on cardiovascular function. This study aimed to investigate a chronic stage after myocardial infarction (MI) and the potential therapeutic effects of delivering a human IGF-1 gene by tissue-engineered bioartificial muscles (BAMs) following coronary artery ligation in Sprague-Dawley rats. Ligation of the left coronary artery or sham operation was performed. Primary skeletal myoblasts were retrovirally transduced to synthesize and secrete recombinant human insulin-like growth factor-1 (rhIGF-1), and green fluorescent protein (GFP), and tissue-engineered into implantable BAMs. The rats that underwent ligation were randomly assigned to 2 groups: MI-IGF group (n = 6) and MI-GFP group (n = 6). The MI-IGF group received rhIGF-secreting BAM (IGF-BAMs) transplantation, and the MI-GFP group received GFP-secreting BAM (GFP-BAMs) transplantation. Another group of rats served as the sham operation group, which was also randomly assigned to 2 subgroups: S-IGF group (n = 6) and S-GFP group (n = 6). The S-IGF group underwent IGF-1-BAM transplantation, and S-GFP group underwent GFP-BAM transplantation. IGF-1-BAMs and GFP-BAMs were implanted subcutaneously into syngeneic rats after two weeks of operation was performed. Four weeks after the treatment, hemodynamics was performed. IGF-1 was measured by radioimmunoassay, and then the rats were sacrificed and ventricular samples were subjected to immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of bax and Bcl-2. TNF-α and caspase 3 expression in myocardium was examined by Western blotting. Primary rat myoblasts were retrovirally transduced to secrete rhIGF-1 and tissue-engineered into implantable BAMs containing parallel arrays of postmitotic myofibers. In vitro, they secreted consistent levels of hIGF (0.4 - 1.2 µg×BAM(-1)×d(-1)). When implanted into syngeneic rat, IGF-BAMs secreted and delivered rhIGF. Four weeks after therapy, the hemodynamics was improved significantly in MI rats treated with IGF-BAMs compared with those treated with GFP-BAMs. The levels of serum IGF-1 were increased significantly in both MI and sham rats treated with IGF-BAM. The mRNA expression of bax was lower and Bcl-2 expression was higher in MI-IGF group than MI-GFP group (P < 0.05). Western blotting assay showed TNF-α and caspase 3 expression was lower in MI-IGF group than MI-GFP group after therapy. rhIGF-1 significantly improves left ventricular function and suppresses cardiomyocyte apoptosis in rats with chronic heart failure. Genetically modified tissue-engineered BAMs provide a method delivering recombinant protein for the treatment of heart failure.

Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

PubMed Central

Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

2013-01-01

Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

Paired evaluation of calvarial reconstruction with prototyped titanium implants with and without ceramic coating.

PubMed

Calderoni, Davi Reis; Gilioli, Rovilson; Munhoz, André Luiz Jardini; Maciel Filho, Rubens; Zavaglia, Cecília Amélia de Carvalho; Lambert, Carlos Salles; Lopes, Eder Socrates Najar; Toro, Ivan Felizardo Contrera; Kharmandayan, Paulo

2014-09-01

To investigate the osseointegration properties of prototyped implants with tridimensionally interconnected pores made of the Ti6Al4V alloy and the influence of a thin calcium phosphate coating. Bilateral critical size calvarial defects were created in thirty Wistar rats and filled with coated and uncoated implants in a randomized fashion. The animals were kept for 15, 45 and 90 days. Implant mechanical integration was evaluated with a push-out test. Bone-implant interface was analyzed using scanning electron microscopy. The maximum force to produce initial displacement of the implants increased during the study period, reaching values around 100N for both types of implants. Intimate contact between bone and implant was present, with progressive bone growth into the pores. No significant differences were seen between coated and uncoated implants. Adequate osseointegration can be achieved in calvarial reconstructions using prototyped Ti6Al4V Implants with the described characteristics of surface and porosity.

CARDIOVASCULAR AND THERMOREGULATORY RESPONSES OF UNRESTRAINED RATS EXPOSED TO FILTERED OR UNFILTERED DIESEL EXHAUST

EPA Science Inventory

Diesel exhaust (DE) has been associated with adverse cardiovascular and pulmonary health effects. The relative contributions of the gas-phase and particulate (PM) components of DE are less well understood. We exposed WKY rats with or without implanted radiotransmitters to air or ...

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

NASA Astrophysics Data System (ADS)

Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

2013-02-01

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

Hydroxyapatite Coating on TiO₂ Nanotube by Sol-Gel Method for Implant Applications.

PubMed

Lim, Hyun-Pil; Park, Sang-Won; Yun, Kwi-Dug; Park, Chan; Ji, Min-Kyung; Oh, Gye-Jeong; Lee, Jong-Tak; Lee, Kwangmin

2018-02-01

The aim of this study was to determine the effect of hydroxyapatite (HA) coating on titanium dioxide (TiO2) nanotube by sol-gel process on viability of osteoblast like cell (MC3T3-E1) and bone formation in rat tibia. Specimens were divided into three groups including commercially pure titanium (control group), TiO2 nanotubes (group N), and HA coated TiO2 nanotubes (group HN). Surface characteristics were determined using field emission scanning electron microscope (FE-SEM; S-4700, Hitachi, Japan) and contact angles were measured. Cell viability was investigated in vitro after 1 day, 3 days, and 7 days of incubation. Implants (2.0 mm in diameter and 5.0 mm in length) were inserted into the tibia of rats. After 4 weeks, histomorphometric analysis was performed. Both N and HN groups showed enhanced hydrophilicity compared to control group. After 7 days of implantation, group HN showed higher cell viability with marginal significance (0.05 < P < 0.1). Bone to implant contact (BIC) ratio in the control group, group N, and group HN were 32.5%, 33.1%, and 43.8%, respectively. Results of this study showed that HA coated TiO2 nanotube using sol-gel process could be used to enhance hydrophilicity and improve osseointegration of dental implant surface.

Non-restraining EEG Radiotelemetry: Epidural and Deep Intracerebral Stereotaxic EEG Electrode Placement.

PubMed

Papazoglou, Anna; Lundt, Andreas; Wormuth, Carola; Ehninger, Dan; Henseler, Christina; Soós, Julien; Broich, Karl; Weiergräber, Marco

2016-06-25

Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies. This powerful technique does not only provide valuable insights into the underlying pathophysiological mechanisms, i.e., the etiopathogenesis of CNS related diseases, it also facilitates the development of new translational, i.e., therapeutic approaches. Whereas competing techniques that make use of recorder systems used in jackets or tethered systems suffer from their unphysiological restraining to semi-restraining character, radiotelemetric EEG recordings overcome these disadvantages. Technically, implantable EEG radiotelemetry allows for precise and highly sensitive measurement of epidural and deep, intracerebral EEGs under various physiological and pathophysiological conditions. First, we present a detailed protocol of a straight forward, successful, quick and efficient technique for epidural (surface) EEG recordings resulting in high-quality electrocorticograms. Second, we demonstrate how to implant deep, intracerebral EEG electrodes, e.g., in the hippocampus (electrohippocampogram). For both approaches, a computerized 3D stereotaxic electrode implantation system is used. The radiofrequency transmitter itself is implanted into a subcutaneous pouch in both mice and rats. Special attention also has to be paid to pre-, peri- and postoperative treatment of the experimental animals. Preoperative preparation of mice and rats, suitable anesthesia as well as postoperative treatment and pain management are described in detail.

Cardiac Conduction through Engineered Tissue

PubMed Central

Choi, Yeong-Hoon; Stamm, Christof; Hammer, Peter E.; Kwaku, Kevin F.; Marler, Jennifer J.; Friehs, Ingeborg; Jones, Mara; Rader, Christine M.; Roy, Nathalie; Eddy, Mau-Thek; Triedman, John K.; Walsh, Edward P.; McGowan, Francis X.; del Nido, Pedro J.; Cowan, Douglas B.

2006-01-01

In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal’s natural life. Perfusion of hearts with fluorescently labeled lectin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding recipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy. PMID:16816362

Reproductive effects of Ficus asperifolia (Moraceae) in female rats.

PubMed

Watcho, Pierre; Ngadjui, Esther; Alango, Nkeng-Efouet P; Benoît, Nguelefack T; Kamanyi, Albert

2009-03-01

The reproductive effects of Ficus asperifolia in female rats were investigated in the present study. Sperm-positive adult female rats were orally administered (P.O.) either the aqueous and methanol extracts of Ficus asperifolia (100 and 500mg/kg), distilled water (10ml/kg) or 5%Tween 80 (10ml/kg) for seven days. On day 10 of pregnancy, the implantation sites were recorded. In the fertility study, adult female rats received the same test substances for 21 days and, the fertility index and litter size determined. In the uterotrophic test, normal and ovariectomized immature rats were treated for seven days with the dry extract of Ficus asperifolia (100 and 500mg/kg) in the absence and presence of 17ȃ-estradiol benzoate 1µg/animal/day, s.c. On day 8, the uterine growth index was measured. Results of the study showed a significant increase (p<0.05) in the implantation sites and litter size of animals receiving 100mg/kg of the aqueous extract of Ficus asperifolia. In the estrogenic assay, normal immature rats were sensitive to the treatment with Ficus asperifolia than the ovariectomized ones. Our results give added scientific support to the popular use of Ficus asperifolia in the treatment of some cases of women's sterility/infertility related problems.

A Fully Implantable Stimulator With Wireless Power and Data Transmission for Experimental Investigation of Epidural Spinal Cord Stimulation.

PubMed

Xu, Qi; Hu, Dingyin; Duan, Bingyu; He, Jiping

2015-07-01

Epidural spinal cord stimulation (ESCS) combined with partial weight-bearing therapy (PWBT) has been shown to facilitate recovery of functional walking for individuals after spinal cord injury (SCI). The investigation of neural mechanisms of recovery from SCI under this treatment has been conducted broadly in rodent models, yet a suitable ESCS system is still unavailable. This paper describes a practical, programmable, and fully implantable stimulator for laboratory research on rats to explore fundamental neurophysiological principles for functional recovery after SCI. The ESCS system is composed of a personal digital assistant (PDA), an external controller, an implantable pulse generator (IPG), lead extension, and stimulating electrodes. The stimulation parameters can be programmed and adjusted through a graphical user interface on the PDA. The external controller is placed on the rat back and communicates with the PDA via radio-frequency (RF) telemetry. An RF carrier from the class-E power amplifier in the external controller provides both data and power for the IPG through an inductive link. The IPG is built around a microcontroller unit to generate voltage-regulated pulses delivered to the bipolar electrode for ESCS in rats. The encapsulated IPG measures 22 mm × 23 mm × 7 mm with a mass of  ∼  3.78 g. This fully implantable batteryless stimulator provided a simplified and efficient method to carry out chronic experiments in untethered animals for medical electro-neurological research.

Characterization of flexible ECoG electrode arrays for chronic recording in awake rats

PubMed Central

Yeager, John D.; Phillips, Derrick J.; Rector, David M.; Bahr, David F.

2008-01-01

We developed a 64 channel flexible polyimide ECoG electrode array and characterized its performance for long term implantation, chronic cortical recording and high resolution mapping of surface evoked potentials in awake rats. To achieve the longest possible recording periods, the flexibility of the electrode array, adhesion between the metals and carrier substrate, and biocompatibility was critical for maintaining the signal integrity. Experimental testing of thin film adhesion was applied to a gold – polyimide system in order to characterize relative interfacial fracture energies for several different adhesion layers, yielding an increase in overall device reliability. We tested several different adhesion techniques including: gold alone without an adhesion layer, titanium-tungsten, tantalum and chromium. We found the titanium-tungsten to be a suitable adhesion layer considering the biocompatibility requirements as well as stability and delamination resistance. While chromium and tantalum produced stronger gold adhesion, concerns over biocompatibility of these materials require further testing. We implanted the polyimide ECoG electrode arrays through a slit made in the skull of rats and recorded cortical surface evoked responses. The arrays performed reliably over a period of at least 100 days and signals compared well with traditional screw electrodes, with better high frequency response characteristics. Since the ultimate goal of chronically implanted electrode arrays is for neural prosthetic devices that need to last many decades, other adhesion layers that would prove safe for implantation may be tested in the same way in order to improve the device reliability. PMID:18640155

The Protective Role of Dexpanthenol on the Endometrial Implants in an Experimentally Induced Rat Endometriosis Model.

PubMed

Soylu Karapinar, Oya; Pinar, Neslihan; Özgür, Tümay; Özcan, Oğuzhan; Bayraktar, H Suphi; Kurt, Raziye Keskin; Nural, Orhan

2017-02-01

Dexpanthenol (Dxp), antioxidant and anti-inflammatory agent, plays an important role in the repair systems against oxidative stress and inflammatory response. The objective of this study is to determine the effect of Dxp on experimental endometriosis model. A prospective experimental study was conducted in Experimental Animal Laboratory of Mustafa Kemal University, Hatay. Twenty nonpregnant female Wistar albino rats, in which experimental model of endometriosis was surgically induced, were randomly divided into 2 groups. Group 1 was administered 500 mg/kg/d Dxp intraperitoneally for 14 days, and group 2 was given the same amount of saline solution. After 2 weeks of medication, the rats were killed and implant volumes, histopathologic scores; and levels of serum total antioxidant status, total oxidant status (TOS), and oxidative stress index (OSI) were evaluated. Plasma and peritoneal fluid levels of tumor necrosis factor α (TNF-α) were analyzed. The endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values were significantly decreased ( P < .05) in the Dxp group compared to the control group. Plasma and peritoneal fluid TNF-α levels were significantly decreased ( P < .05) in the Dxp group compared to the control group. Dexpanthenol has free radical scavenger effects, and antioxidant properties has significantly regressed endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values. Serum and peritoneal fluid TNF-α levels were significantly decreased in the Dxp group. So Dxp decreased oxidative stress.

Effects of a sustained-release naloxone pellet on luteinizing hormone secretion in female rats.

PubMed

Gabriel, S M; Simpkins, J W

1983-11-01

Studies were undertaken to develop a naloxone implant capable of chronically blocking opioid receptors for several weeks in an effort to evaluate the effect of this prolonged narcotic antagonism on luteinizing hormone (LH) secretion in female rats. Antagonism of opiate receptors was achieved with a tablet formulation which contained 75 mg naloxone free base and a high content of the insoluble binding material, Mg stearate. Subcutaneous placement of this implant prevented morphine-induced analgesia for 2 weeks and antagonized the LH suppressory effects of morphine (15 or 30 mg/kg) administration. Thus, this naloxone delivery system is capable of chronically occupying the opioid receptors which mediate morphine's effects on analgesia and LH secretion. Despite this, the naloxone pellet only moderately enhanced the initial rate of increase in LH secretion following ovariectomy (day 1) and was ineffective in further augmenting LH secretion at 3 and 7 days after implantation. In rats which were ovariectomized and implanted immediately with estradiol-containing Silastic capsules, the naloxone pellet was ineffective in altering LH secretion 1, 3 or 7 days later. Thus, while chronic exposure to naloxone persistently antagonizes the pharmacologic actions of morphine, the naloxone pellet only transiently blocked the tonic inhibitory effect of endogenous opioid peptides. The mechanism by which the LH secretory effects of naloxone are lost following chronic exposure to the antagonist are at present unknown, but may involve the activation of compensatory mechanisms which are inhibitory to LH secretion.

Alkaline biodegradable implants for osteoporotic bone defects--importance of microenvironment pH.

PubMed

Liu, W; Wang, T; Yang, C; Darvell, B W; Wu, J; Lin, K; Chang, J; Pan, H; Lu, W W

2016-01-01

Change of microenvironment pH by biodegradable implants may ameliorate unbalanced osteoporotic bone remodeling. The present work demonstrated that a weak alkaline condition stimulated osteoblasts differentiation while suppressed osteoclast generation. In vivo, implants with an alkaline microenvironment pH (monitored by a pH microelectrode) exhibited a promising healing effect for the repair of osteoporotic bone defects. Under osteoporotic conditions, the response of the bone microenvironment to an endosseous implant is significantly impaired, and this substantially increases the risk of fracture, non-union and aseptic implant loosening. Acid-base equilibrium is an important factor influencing bone cell behaviour. The present purpose was to study the effect of a series of alkaline biodegradable implant materials on regeneration of osteoporotic bone defect, monitoring the microenvironment pH (μe-pH) over time. The proliferation and differentiation potential of osteoporotic rat bone marrow stromal cells and RAW 264.7 cells were examined under various pH conditions. Ovariectomized rat bone defects were filled with specific biodegradable materials, and μe-pH was measured by pH microelectrode. New osteoid and tartrate-resistant acid phosphatase-positive osteoclast-like cells were examined by Goldner's trichrome and TRAP staining, respectively. The intermediate layer between implants and new bone were studied using energy-dispersive X-ray spectroscopy (EDX) linear scanning. In vitro, weak alkaline conditions stimulated osteoporotic rat bone marrow stromal cells (oBMSC) differentiation, while inhibiting the formation of osteoclasts. In vivo, μe-pH differs from that of the homogeneous peripheral blood and exhibits variations over time particular to each material. Higher initial μe-pH was associated with more new bone formation, late response of TRAP-positive osteoclast-like cells and the development of an intermediate 'apatitic' layer in vivo. EDX suggested that residual material may influence μe-pH even 9 weeks post-surgery. The pH microelectrode is suitable for in vivo μe-pH detection. Alkaline biodegradable materials generate an in vivo microenvironmental pH which is higher than the normal physiological value and show promising healing effects in the context of osteoporotic bone defects.

[Bone defect replacement under conditions of transosseous osteosynthesis and titanium nickelide implant application].

PubMed

Ir'ianov, Iu M; Ir'ianova, T Iu

2012-01-01

In the experiment conducted on 30 Wistar rats, the peculiarities of tibial bone defect replacement under conditions of transosseous osteosynthesis and implantation of titanium nickelide mesh structures were studied using the methods of scanning electron microscopy and x-ray electron probe microanalysis. It was demonstrated that implant osseointegration occured 7 days after surgery, and after 30 days the defect was replaced with bone tissue by the type of primary bone wound healing, thus the organotypical remodeling of regenerated bone took place.

Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats.

PubMed

Kandasamy, Ram; Lee, Andrea T; Morgan, Michael M

2017-12-01

The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats. Adult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase. Administration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats. These data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

PubMed

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-03-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation.

Angiotensin II enhancement during pregnancy influences the emotionality of rat offspring (Rattus norvegicus) in adulthood. Potential use of the Rat Grimace Scale.

PubMed

Senko, Tomas; Olexova, Lucia; Mokosakova, Miroslava; Kršková, Lucia

2017-05-01

One of the systems, which can be prenatally reprogrammed, is the renin-angiotensin-aldosterone system (RAAS). The aim of our experiment was to determine how prenatal activation of RAAS via exposure to elevated levels of angiotensin II (Ang II) influences the rat offspring's emotionality. Pregnant female rats were implanted with osmotic minipumps that continually released Ang II and oval object of the same shape and size was implanted into control dams. The adult offspring (AngII and control groups) were tested in rat grimace scale (RGS), open field test (OF) and elevated plus maze (EPM). Psychological stress increased the RGS score in both groups of animals. AngII animals had significantly lower RGS score (i.e. less negative emotions) in the home cage but higher index of emotional reactivity in RGS. AngII animals had also significantly lower frequency of defecation in OF and had no effect on changes in anxiety-like behaviour. We concluded that maternal activation of RAAS modified some aspect of emotionality of experimental animals and led to an enhanced emotional response to stress situation.

In situ ultrasound imaging of silk hydrogel degradation and neovascularization.

PubMed

Leng, Xiaoping; Liu, Bin; Su, Bo; Liang, Min; Shi, Liangchen; Li, Shouqiang; Qu, Shaohui; Fu, Xin; Liu, Yue; Yao, Meng; Kaplan, David L; Wang, Yansong; Wang, Xiaoqin

2017-03-01

Ultrasound (US) is a useful technique to monitor morphological and functional changes of biomaterial implants without sacrificing the animal. Contrast-enhanced ultrasound (CEUS) along with two-dimensional (2D) US were used to characterize the biodegradation and neovascularization of silk protein (8 wt%) hydrogel implants in rats. Cylinder-shaped silk hydrogel plugs were implanted into the space between the hind limb thigh muscles in Wistar rats (n = 6). The increase of echogenicity in 2D US revealed tissue-ingrowth-accompanied gel degradation over 18 weeks. The shape and size of the implanted gels remained qualitatively unchanged until week 15, as confirmed by Bland and Altman analysis and visualization of retrieved samples. Using CEUS, neovascularization was monitored by the presence of microbubbles in the gel area, and the dynamic vascularization process was indicated by the contrast enhancement values, which showed a relatively low level (< 5 dB) during weeks 1-8 and significantly increased levels (around 20 dB at week 15 and > 35 dB at week 18), suggesting that major vascularization had occurred in the gel implants by this time point. Histological and scanning electron microscopic analysis of explants revealed time-dependent increases in the pore size of the gel matrix, the presence of endothelial and red blood cells and the number of blood vessels in the gel implants, indicating that degradation and vascularization did occur in silk gel implants during the time period. The present study demonstrates the use of US imaging for monitoring of in vivo degradation and vascularization of silk implants in a non-destructive way. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Cytokine induction of sol–gel-derived TiO2 and SiO2 coatings on metallic substrates after implantation to rat femur

PubMed Central

Urbanski, Wiktor; Marycz, Krzysztof; Krzak, Justyna; Pezowicz, Celina; Dragan, Szymon Feliks

2017-01-01

Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant–tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS) and titanium alloy (Ti6Al4V) biomaterials coated with titanium dioxide (TiO2) and silica (SiO2) coatings prepared by sol–gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone–implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software) of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol–gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues, irrespective of the material used as a substrate, that is, either Ti6Al4V or SS. This suggests lower inflammatory response, which directly points out improvement of materials’ biocompatibility. PMID:28280331

[A study of bone-like apatite formation on calcium phosphate ceramics in different kinds of animals in vivo].

PubMed

Duan, Yourong; Wu, Yao; Wang, Chaoyuan; Chen, Jiyong; Zhang, Xingdong

2003-03-01

Bone-like apatite formation on the surface of calcium phosphate ceramics has been believed to be necessary for new bone to grow on the ceramics and to be related to the osteoinductivity of the material. The research of bone-like apatite formation is a great help to understanding the mechanism of osteoinduction. Synthetic porous calcium phosphate ceramics (HA/TCP = 70/30) were implanted intramuscularly in pigs, dogs, rabbits and rats to make a comparative study of the bone-like apatite formation onto the porous HA/TCP ceramics in different animals. Specimens were harvested at 14 days after implantation. Samples were detected for the surface morphology with SEM. The chemical composition of the sample surface after implantation was analyzed with reflection infrared (R-IR). Obvious bone-like apatite formation could be detected in the sections of porous specimens harvested from all animals after 14 days intramuscular implantation. Crystal deposition could be only observed on the surface of the concave regions of the samples collected from dogs, rabbits and rat. On the contrary, evenly distributed flake-shaped crystal could be found on the pore surface and also on the outer surface of the materials implanted in pigs. The morphology of bone-like apatite in pigs was different from that in the others animals. Bone-like apatite was not observed in dense specimen implanted intramuscularly. Bone-like apatite formed faster on specimens implanted in rabbit than that in other animals. This formation sequence is different from the sequence of osteoinductivity of biphasic calcium phosphate ceramics implanted in these animals. The results demonstrated that the formation of bone-like apatite on materials is a prerequisite condition to their osteoinduction but other factors also play important roles in osteoinduction.

Analysis of 30 breast implant rupture cases.

PubMed

Tark, Kwan Chul; Jeong, Hii Sun; Roh, Tae Suk; Choi, Jong Woo

2005-01-01

Breast implants used for augmentation mammoplasty or breast reconstruction could rupture from various causes such as trauma or spontaneous failure. The objectives of this study were to investigate the relationships between the causes of implant rupture and the degree of capsular contracture, and then to evaluate the relative efficacies of specific signs on magnetic resonance imaging (MRI) known to be beneficial for diagnosing the rupture. A retrospective review identified patients with prosthetic implant rupture or impending rupture treated by the senior author. The 30 cases of implant rupture available for review were classified into two groups: intracapsular and extracapsular ruptures. The 30 cases of breast implant ruptures were analyzed with respect to the clinical symptoms and signs, the causes of rupture, the degree of capsular contracture, and therapeutic plans. Among the 30 cases, 14 patients who had undergone MRI during the diagnostic period were analyzed with respect to the relationships between MRI readings and operative findings. Spontaneous rupture of membranes was most common (80%), followed by failure because of trauma (7%) and valve or implant base (4%). The symptoms during implant rupture were contour deformity, palpated mass-like lesions, pain, and focal inflammation. According to the analysis of specific MRI signs, the sensitivity and specificity of the linguine sign were 87% and 100%, respectively, for intracapsular rupture. For extracapsular rupture, the sensitivity and specificity of the linguine sign were, respectively, 67% and 75%. The sensitivity and specificity of the rat-tail sign and tear drop sign were 14% and 50%, respectively. Breast implant rupture was correlated with the degree of capsular contracture in our study. Among the various specific MRI signs used in diagnosing the rupture, the linguine sign was reliable and had a high sensitivity and specificity, especially in cases of intracapsular rupture. On the other hand, the rat-tail and tear drop signs were nonspecific signs for diagnosing the rupture of breast implant.

Sclerostin-neutralizing Antibody Enhances Bone Regeneration around Oral Implants.

PubMed

Yu, Shan Huey; Hao, Jie; Fretwurst, Tobias; Liu, Min; Kostenuik, Paul; Giannobile, William V; Jin, Qiming

2018-06-19

Dental implants have been an important option for the replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. Monoclonal antibody against sclerostin (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model. To investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after the extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1x2 mm custom titanium implants were pressed-fitted into the osteotomies. Coincident with initial implant placement, Scl-Ab or vehicle was administered subcutaneously twice weekly at a dose of 25 mg/kg for 10-28 days and compared to a vehicle control. Rats were sacrificed 10, 14 and 28d after surgery, and maxillae were harvested and analyzed by micro-computed tomography (microCT), histology and histomorphometry. MicroCT analysis demonstrated that maxillary bone volume fraction was approximately 2 to 2.5-fold greater in Scl-Ab treated animals as compared to vehicle alone at days 14 and 28. Consistent with those findings, 2-D bone fill percentage within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28d. In addition, bone-implant contact at 28d was approximately 2-fold greater in the Scl-Ab group compared to vehicle controls. These results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone regeneration at alveolar bone defects, and to enhance dental implant osseointegration.

Di-n-butyl phthalate prompts interruption of spermatogenesis, steroidogenesis, and fertility associated with increased testicular oxidative stress in adult male rats.

PubMed

Nelli, Giribabu; Pamanji, Sreenivasula Reddy

2017-08-01

Di-n-butyl phthalate (DBP) is extensively used as plasticizer, and it was ubiquitary released into the environment. The present study was aimed to investigate the effect of DBP on reproductive competence in adult male rats. Adult male rats were received corn oil or DBP injection intraperitoneally (ip) at 100 and 500 mg/kg body weight on 90, 97, 104, and 111 days. Following completion of the experimental period, adult male rats were cohabitated with untreated proestrus female rats for determination of fertilization capacity. Then, adult male rats were sacrificed, and other reproductive endpoints were determined by histopathology and biochemical analysis. The results revealed significant reduction of fertilization potential by decrease mating, fertility indices with increase pre-implantation and post-implantation losses, and resorptions in normal female rat cohabitation with DBP-treated adult male rats. The testes, seminal vesicle tissue somatic indices, epididymal sperm count, motility, viability, and hypoosmotic swelling (HOS) sperm were significantly decreased with increased sperm morphological abnormalities in DBP-treated adult male rats. The disorientation of spermatogenic cells decreased the diameter and epithelial thickness of seminiferous tubule in the testicular histopathology of DBP-exposed rats. Significant reduction of testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase enzyme levels and serum testosterone with increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were observed in DBP-treated groups. Higher testicular oxidative stress marker (lipid peroxidation product) with lower antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase levels in DBP-exposed groups was observed. From these results, it can be concluded that DBP increases oxidative stress; it leads to impairment of spermatogenesis, steroidogenesis, and fertility in adult male rats.

Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex

NASA Astrophysics Data System (ADS)

Wang, Chun; Brunton, Emma; Haghgooie, Saman; Cassells, Kahli; Lowery, Arthur; Rajan, Ramesh

2013-08-01

Objective. Cortical neural prostheses with implanted electrode arrays have been used to restore compromised brain functions but concerns remain regarding their long-term stability and functional performance. Approach. Here we report changes in electrode impedance and stimulation thresholds for a custom-designed electrode array implanted in rat motor cortex for up to three months. Main Results. The array comprises four 2000 µm long electrodes with a large annular stimulating surface (7860-15700 µm2) displaced from the penetrating insulated tip. Compared to pre-implantation in vitro values there were three phases of impedance change: (1) an immediate large increase of impedance by an average of two-fold on implantation; (2) a period of continued impedance increase, albeit with considerable variability, which reached a peak at approximately four weeks post-implantation and remained high over the next two weeks; (3) finally, a period of 5-6 weeks when impedance stabilized at levels close to those seen immediately post-implantation. Impedance could often be temporarily decreased by applying brief trains of current stimulation, used to evoke motor output. The stimulation threshold to induce observable motor behaviour was generally between 75-100 µA, with charge density varying from 48-128 µC cm-2, consistent with the lower current density generated by electrodes with larger stimulating surface area. No systematic change in thresholds occurred over time, suggesting that device functionality was not compromised by the factors that caused changes in electrode impedance. Significance. The present results provide support for the use of annulus electrodes in future applications in cortical neural prostheses.

Expression of anti-Müllerian hormone in two rat models of polycystic ovary syndrome.

PubMed

Du, Dan-Feng; Li, Xue-Lian; Zheng, Sai-Hua

2016-12-01

Anti-Müllerian hormone (AMH) levels are two to three times higher in patients with polycystic ovary syndrome (PCOS), but the mechanism of increased AMH levels in PCOS remains unclear. The purpose of our experiment was to investigate a change in AMH levels in two kinds of commonly used rat models and to determine an ideal model for future research of AMH in the pathogenesis of PCOS. Thirty female Sprague Dawley rats were treated using two modeling methods: implantation of a levonorgestrel silastic implant or injection with sodium prasterone sulfate plus human chorionic gonadotropin (hCG). Rats in the control group were implanted with a blank silastic stick. Serum steroid concentrations, ovarian morphology and ovarian expression of AMH and AMH-receptor II (RII) proteins were determined and their correlations were studied. The results from the levonorgestrel and hCG group were closer to those displayed by human PCOS patients than the sodium prasterone sulfate and hCG group. Ovarian local expression of AMH and AMH-RII was increased in these both models compared with the control group; however, an elevation of serum AMH concentration was not observed (12.53 ± 0.99 ng/ml and 13.22 ± 1.09 ng/ml vs 16.30 ± 0.98 ng/ml). The levonorgestrel and hCG model is more suitable for the study of PCOS in puberty. © 2016 Japan Society of Obstetrics and Gynecology.

Wistar rats immature testicular tissue vitrification and heterotopic grafting.

PubMed

Benvenutti, Larissa; Salvador, Rafael Alonso; Til, David; Senn, Alfred Paul; Tames, David Rivero; Amaral, Nicole Louise Lângaro; Amaral, Vera Lúcia Lângaro

2018-04-25

To evaluate the efficiency of two vitrification protocols for rat immature testicular tissue and heterotopic transplantation. Twenty-four pre-pubertal Wistar rats were divided into three groups (n=8). After orchiectomy, testicular fragments (3mm) from Groups 1 and 2 were vitrified with different cryoprotectant concentration solutions, using sterile inoculation loops as support. After warming up, the fragments were submitted to cell viability assessment by Trypan blue and histological evaluation. Vitrified (Groups 1 and 2) and fresh (Group 3) fragments were grafted to the animals periauricular region. After 8 weeks of grafting, the implant site was histologically analyzed. The viability recovery rate from Group 1 (72.09%) was higher (p=0.02) than that from Group 2 (59.19%). Histological analysis showed similar tubular integrity between fresh fragments from Groups 1 and 3. Group 2 samples presented lower tubular integrity. We ran histological analyses in the grafts from the Groups. In all groups, it was possible to see the implant site, however, no fragment of testicular tissue or signs of inflammation were histologically found in most samples from Groups 1 and 3. In one sample from Group 2, we found degenerated seminiferous tubules with necrosis and signs of an inflammatory process. In another sample from Group 2, we found seminiferous tubules in the implant site. The vitrification of pre-pubertal testicular tissue of rats showed little damage to cell viability through histological analysis when we used cryoprotectants in a lower concentration. Heterotopic transplantation could not preserve the structural organization of the testicular tissue.

Enhanced antitumor efficacy on hepatoma-bearing rats with adriamycin-loaded nanoparticles administered into hepatic artery.

PubMed

Chen, Jiang-Hao; Ling, Rui; Yao, Qing; Wang, Ling; Ma, Zhong; Li, Yu; Wang, Zhe; Xu, Hu

2004-07-01

To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats. NADR was prepared by the interfacial polymerization method. Walker-256 carcinosarcomas were surgically implanted into the left liver lobes of 60 male Wistar rats, which were divided into 4 groups at random (15 rats per group). On the 7th day after implantation, normal saline (NS), free ADR (FADR), NADR, or ADR mixed with unloaded nanoparticles (ADR+NP) was respectively injected via the hepatic artery (i.a.) of rats in different groups. The dose of ADR in each formulation was 2.0 mg/kg body weight and the concentration was 1.0 mg/mL. Survival time, tumor enlargement ratio, and tumor necrosis degree were compared between each group. Compared with the rats that received NS i.a., the rats that received FADR or ADR+NP acquired apparent inhibition on tumor growth, as well as prolonged their life span. Further significant anticancer efficacy was observed in rats that received i.a. administration of NADR. Statistics indicated that NADR brought on a more significant tumor inhibition and more extensive tumor necrosis, as compared to FADR or ADR+NP. The mean tumor enlargement ratio on the 7th day after NADR i.a. was 1.106. The mean tumor-bearing survival time was 39.50 days. Prolonged life span ratio was 109.22% as compared with rats that accepted NS. Therapeutic effect of ADR on liver malignancy can be significantly enhanced by its nanopaticle formulation and administration via hepatic artery.

Impact of Focused Ultrasound-enhanced Drug Delivery on Survival in Rats with Glioma

NASA Astrophysics Data System (ADS)

Treat, Lisa Hsu; Zhang, Yongzhi; McDannold, Nathan; Hynynen, Kullervo

2009-04-01

Malignancies of the brain remain difficult to treat with chemotherapy because the selective permeability of the blood-brain barrier (BBB) blocks many potent agents from reaching their target. Previous studies have illustrated the feasibility of drug and antibody delivery across the BBB using MRI-guided focused ultrasound. In this study, we investigated the impact of focused ultrasound-enhanced delivery of doxorubicin on survival in rats with aggressive glioma. Sprague-Dawley rats were implanted with 9 L gliosarcoma cells in the brain. Eight days after implantation, each rat received one of the following: (1) no treatment (control), (2) a single treatment with microbubble-enhanced MRI-guided focused ultrasound (FUS only), (3) a single treatment with i.v. liposomal doxorubicin (DOX only), or (4) a single treatment with microbubble-enhanced MRI-guided focused ultrasound and concurrent i.v. injections of liposomal doxorubicin (FUS+DOX). The survival time from implantation to death or euthanasia was recorded. We observed a modest but significant increase in median survival time in rats treated with combined MRI-guided focused ultrasound chemotherapy, compared to chemotherapy alone (p<0.001). There was no significant improvement in survival between those who received stand-alone chemotherapy and those who did not receive any treatment (p>0.10). Our study demonstrates for the first time a therapeutic benefit achieved with ultrasound-enhanced drug delivery across the blood-brain barrier. This confirmation of efficacy in an in vivo tumor model indicates that targeted drug delivery using MRI-guided focused ultrasound has the potential to have a major impact on the treatment of patients with brain tumors and other neurological disorders.

Aging reduces the neuroprotective capacity, VEGF secretion, and metabolic activity of rat choroid plexus epithelial cells.

PubMed

Emerich, Dwaine F; Schneider, Patricia; Bintz, Briannan; Hudak, Jebecka; Thanos, Christopher G

2007-01-01

Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3-4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells.

Bone Marrow–Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection

PubMed Central

Criman, Erik T.; Kurata, Wendy E.; Matsumoto, Karen W.; Aubin, Harry T.; Campbell, Carmen E.

2016-01-01

Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow–derived MSCs improves infection resistance in vivo after inoculation with Escherichia coli (E. coli). Methods: Rat bone marrow–derived MSCs at passage 3 were seeded onto bovine pericardium and cultured for 7 days before implantation. Additional rats (n = 24) were implanted subcutaneously with MSC-seeded or unseeded mesh and inoculated with 7 × 105 colony-forming units of E. coli or saline before wound closure (group 1, unseeded mesh/saline; group 2, unseeded mesh/E. coli; group 3, MSC-seeded mesh/E. coli; 8 rats per group). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. Results: MSC-seeded meshes inoculated with E. coli demonstrated superior bacterial clearance and preservation of mesh integrity compared with E. coli–inoculated unseeded meshes (87.5% versus 0% clearance; p = 0.001). Complete mesh degradation concurrent with abscess formation was observed in 100% of rats in the unseeded/E. coli group, which is in contrast to 12.5% of rats in the MSC-seeded/E. coli group. Histologic evaluation determined that remodeling characteristics of E. coli–inoculated MSC-seeded meshes were similar to those of uninfected meshes 4 weeks after implantation. Conclusions: Augmenting a bioprosthetic material with stem cells seems to markedly enhance resistance to bacterial infection in vivo and preserve mesh integrity. PMID:27482490

Evaluation of Musa (Paradisiaca Linn. cultivar)--"Puttubale" stem juice for antilithiatic activity in albino rats.

PubMed

Prasad, K V; Bharathi, K; Srinivasan, K K

1993-10-01

The fresh juice of Musa stem (Puttubale) was tested for its antilithiatic activity. Zinc discs were implanted in the urinary bladder of albino rats to induce urolithiasis. The stones formed were mainly of magnesium ammonium phosphate with traces of calcium oxalate. Musa stem juice (3 mL/rat/day orally) was found to be effective in reducing the formation and also in dissolving the pre-formed stones.

Different critical perinatal periods and hypothalamic sites of oestradiol action in the defeminisation of luteinising hormone surge and lordosis capacity in the rat.

PubMed

Sakakibara, M; Deura, C; Minabe, S; Iwata, Y; Uenoyama, Y; Maeda, K-I; Tsukamura, H

2013-03-01

Female rats show a gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E(2) ) or administration of an NMDA antagonist, were examined for their ability to show an E(2) -induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol-benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E(2) -induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2-induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E(2) implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E(2) -induced LH surge in female rats, whereas E(2) implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E(2) implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen-induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from that of sexual behaviour, in terms of the site(s) of oestrogen action and critical period, as well as the neurotransmitter system involved. © 2012 British Society for Neuroendocrinology.

Silver oxide-containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur.

PubMed

Eto, Shuichi; Miyamoto, Hiroshi; Shobuike, Takeo; Noda, Iwao; Akiyama, Takayuki; Tsukamoto, Masatsugu; Ueno, Masaya; Someya, Shinsuke; Kawano, Shunsuke; Sonohata, Motoki; Mawatari, Masaaki

2015-09-01

Antibacterial silver with hydroxyapatite (Ag-HA) is a promising coating material for imparting antibacterial properties to implants. We previously reported that 3% (w/w) silver with HA (3% Ag-HA) has both antibacterial activity and osteoconductivity. In this study, we investigated the effects of Ag-HA on the in vitro osteoblast function and the in vivo anchorage strength and osteoconductivity of implants. Production of the osteoblast marker alkaline phosphatase, but not cytotoxicity, was observed in cells of the osteoblast cell line MC3T3-E1 cultured on the 3% Ag-HA-coated surface. These results were similar to those observed with silver-free HA coating. In contrast, a significant high level of cytotoxicity was observed when the cells were cultured on a 50% Ag-HA-coated surface. The anchorage strength of implants inserted into the femur of Sprague-Dawley (SD) rats was enhanced by coating the implants with 3% Ag-HA. On the 3% Ag-HA-coated surface, both metaphyseal and diaphyseal areas were largely covered with new bone and had adequate osteoconductivity. These results suggest that 3% Ag-HA, like conventional HA, promotes osteogenesis by supporting osteoblast viability and function and thereby contributes to sufficient anchorage strength of implants. Application of 3% Ag-HA, which combines the osteoconductivity of HA and the antibacterial activity of silver, to prosthetic joints will help prevent postoperative infections. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The influence of external ultrasound on the histologic architecture of the organic capsule around smooth silicone implants: experimental study in rats.

PubMed

Mendes, F H; Viterbo, F; DeLucca, L

2008-05-01

Capsular contracture is the main complication related to breast silicone implants, and its prevention remains a medical challenge. The authors present experimental research examining the effect of external ultrasound on the formation and contracture of peri-implant capsules. In this study, 42 male Wistar rats had a 2-mm smooth surface implant placed in a dorsal submuscular pocket. They then were separated into "ultrasound" and "control" groups that received repeated external applications either with or without the ultrasound power on. Ultrasound applications were given three times a week for a period of 90 days. After that, both groups were housed under the same conditions with no application scheduled. Five animals of each group, killed at 30, 60, 90, and 180 days, had their implants removed along with the capsule, which received a special histologic preparation via annular sectioning that provided wide circumferential observation of the capsular tissue. Sections were stained with hematoxylin/eosin stain, Masson's trichrome stain, and Pricrosirius Red stain for regular microscopic evaluation under normal and polarized light. Histologic data showed that capsules from the ultrasound and control groups had statistically significant differences. Ultrasound application developed a capsular architecture similar to that shown within textured silicone implants, and its effect had an early definition with subsequent stabilization. The authors conclude that early and repeated external ultrasound application enhances the thickness, cellular count, and vascularity of smooth silicone capsular tissue, whereas it diminishes the pattern of parallel orientation of collagen fibers.

[Transplacental effects of bemithyl].

PubMed

Bugaeva, L I; Denisova, T D; Spasov, A A

2007-01-01

The daily administration of bemithyl (20 mg/kg) from 6 th to 16 th day of pregnancy in female rats led to the decrease in fetal death after the implantation and increased fetal body weight. The treatment of pregnant rats also led to acceleration of the development of physical condition and sensomotor reflexes of progeny in the postnatal period.

GLUCOCORTICOIDS REGULATE THE SYNTHESIS OF GFAP IN INTACT AND ADRENALECTOMIZED RATS BUT DO NOT AFFECT ITS EXPRESSION FOLLOWING BRAIN INJURY

EPA Science Inventory

We examined the effects of corticosterone (CORT) on the amount of glial fibrillary acidic protein (GFAP) in INTACT, adrenalectomized (ADX) and brain-damaged rats. hort (5 days)- to long-term (4 months) CORT administration by injection, pellet implantation, or in the drinking wate...

Prolonged exposure to a low-dose of bisphenol A increases spontaneous motor activity in adult male rats.

PubMed

Nojima, Kazuo; Takata, Tomoyo; Masuno, Hiroshi

2013-07-01

We investigated the effects of bisphenol A (BPA), an environmental endocrine-disrupting chemical, on spontaneous motor activity in adult male rats. The rats were implanted intraperitoneally with mini-osmotic pumps containing either BPA (50 μg/kg body weight per day) in sesame oil (BPA-treated group) or sesame oil only (vehicle-treated group). Spontaneous motor activity during a 24-h period was measured over 5 days from day 9 to day 13 after implantation using an animal movement analysis system. Spontaneous motor activity during the last 2 h of the dark phase and during the first 1-h of the light phase was increased in the BPA-treated group. Total spontaneous motor activity during the 12-h light phase, but not the 12-h dark phase, was higher in the BPA-treated group than in the vehicle-treated group. These findings suggest that BPA may induce hyperactivity in adult male rats during the 12-h light phase, especially during the 2 h immediately preceding sleep-onset and 1 h immediately following sleep-onset.

The effect of microgeometry, implant thickness and polyurethane chemistry on the foreign body response to subcutaneous implants.

PubMed

Ward, W Kenneth; Slobodzian, Emily P; Tiekotter, Kenneth L; Wood, Michael D

2002-11-01

We addressed the effect of implant thickness, implant porosity, and polyurethane (PU) chemistry on angiogenesis and on the foreign body response in rats. The following materials were implanted subcutaneously for 7 weeks then excised for histologic analysis: a solid PU; a solid polyurethane with silicone and polyethylene oxide (PU-S-PEO); porous expanded polytetrafluoroethylene (ePTFE); and porous polyvinyl alcohol sponge (PVA). Two thicknesses of PU-S-PEO were compared: 300 microns (thin) and 2000 microns (thick). Foreign body capsule (FBC) thickness was much less in PU-S-PEO implants than in PU implants. In addition, FBC were thinner in thin implants than in thick implants. FBC was much more dense in solid implants than in porous implants. As compared with solid implants, porous implants (PVA and ePTFE) led to a marked increase in the number of microvessels that developed adjacent to the implant, as observed both with hematoxylin/eosin staining and with an immunohistochemical anti-endothelial stain. We conclude that the polyethylene oxide and silicone moieties in PU reduce the thickness of the subsequent FBC. In addition, thin implants lead to a thin FBC. Porous implants (PVA and ePTFE) cause more angiogenesis than solid implants. These results may have implications for the measurement of blood-derived analytes by biosensors.

Flap preconditioning by pressure-controlled cupping in a rat model.

PubMed

Koh, Kyung S; Park, Sung Woo; Oh, Tae Suk; Choi, Jong Woo

2016-08-01

Flap survival is essential for the success of soft-tissue reconstruction. Accordingly, various surgical and medical methods aim to increase flap survival. Because flap survival is affected by the innate vascular supply, traditional preconditioning methods mainly target vasodilatation or vascular reorientation to increase blood flow to the tissue. External stress on the skin, such as an external volume expander or cupping, induces vascular remodeling, and these approaches have been used in the fat grafting field and in traditional Asian medicine. In the present study, we used a rat random-pattern dorsal flap model to study the effectiveness of preconditioning with an externally applied device (cupping) at the flap site that directly applied negative pressure to the skin. The device, the pressure-controlled cupping, is connected to negative pressure vacuum device providing accurate pressure control from 0 mm Hg to -200 mm Hg. Flap surgery was performed after preconditioning under -25 mm Hg suction pressure for 30 min a day for 5 d, followed by 9 d of postoperative observation. Flap survival was assessed as the area of viable tissue and was compared between the preconditioned group and a control group. The preconditioned group showed absolute percentage increase of flap viability relative to the entire flap by 19.0± 7.6% (average 70.1% versus 51.0%). Tissue perfusion of entire flap, evaluated by laser Doppler imaging system, was improved with absolute percentage increase by 24.2± 10.4% (average 77.4% versus 53.1%). Histologic analysis of hematoxylin and eosin, CD31, and Masson-trichrome staining showed increased vascular density in the subdermal plexus and more organized collagen production with hypertrophy of the attached muscle. Our study suggests that flap preconditioning caused by controlled noninvasive suction induces vascular remodeling that increases tissue perfusion and improves flap survival in a rat model. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing osseointegration of orthopedic implants with titania nanotube surfaces

NASA Astrophysics Data System (ADS)

Baker, Erin A.

Introduction: As joint arthroplasty surgical procedures increase annually, the development of new strategies, including novel materials and surface modifications, to attain solid bone-implant fixation are needed to increase implant terms of service. In this study, we evaluate two morphologies of titania nanotubes in both in vitro and in vivo experiments to quantify osseointegrative potential and material-level biocompatibility. Materials and Methods: Samples were prepared via an electrochemical etching process. Two different titania nanotube (TiNT) morphologies were produced, Aligned and Trabecular. For the in vitro experiment, Sprague Dawley (SD) rat marrow-derived bone marrow cells (BMC) were seeded on samples. Alkaline phosphatase (ALP) activity, osteocalcin (OC) expression, expression of relevant genes as well as cell attachment and morphology were assessed. In the first in vivo experiment, Kirschner wires were implanted unilaterally into SD rat femora with a TiNT-etched or unmodified (Control) implant. General health assessments and weekly body weights were recorded. At a 12-week endpoint, hematologic, systemic metal ion, and histologic analyses were performed. For the second in vivo experiment, Kirschner wires were implanted bilaterally into SD rat femora, with a TiNT-etched implant in one femora and unmodified (Control) implant as an internal control. At 4- and 12-week endpoints, femora were assessed via biomechanics, undecalcified histology, micro-computed tomography (muCT), and backscattered electron imaging (BEI) to characterize de novo bone formation. Results: In vitro experiments demonstrated BMC attachment and differentiation into osteoblasts as well as greater ALP activity, OC expression, total cell counts, and gene expression (of Col1a1, IGF-1, and osteonectin) on TiNT surfaces versus Controls. Cells on TiNT-etched substrates were smaller in diameter and more eccentric than Controls. In the first in vivo experiment, there were significant differences in body weight between groups at Weeks 9 and 11. There were no significant differences in red or white blood cell function between TiNT groups and Control. Aluminum levels in the lungs were significantly greater in the Trabecular TiNT group compared to Control. Histologic analysis showed significantly fewer granulocytes and neutrophils in the distal region of Trabecular TiNT-implanted femora as well as significantly fewer foreign body giant/multinucleated cells and neutrophils in the midshaft region of Aligned TiNT-implanted femora versus Controls. In the second in vivo experiment, at 12 weeks, microCT analysis showed TiNT implants generated greater bone formation than Controls. Histologic analysis demonstrated 1.5 times greater bone-implant contact in TiNT groups than Controls at 12 weeks. TiNT groups exhibited 1.3 to 3.7 times greater strength of fixation than Controls during pull-out testing. Discussion and Conclusions: In vitro data confirmed BMC attachment and differentiation into osteoblasts as well as osteoblastic phenotypic behavior. A clinically-relevant in vivo model of femoral intramedullary fixation, showed increased bone formation and quality in femora implanted with TiNT-etched implants versus Controls. A second in vivo study showed that TiNT surfaces do not generate systemic effects and may beneficially modulate the periprosthetic inflammatory environment.

Amniotic membranes as prosthetic material: experimental utilization data of a rat model.

PubMed

Zachariou, Z

1997-10-01

Prosthetic materials are applied for closing big tissue defects, the repair of traumatized organs, or hernias. Because nonabsorbable synthetic materials are rigid, possess a defined and unchangeable size, and foreign body reaction (FBR) may occur, biological materials may be an alternative. In experimental studies in rats the authors implanted the fetal parts of the human amniotic membranes and examined the utilization and FBR induced in a standardized model. In addition amnion (AM) was combined with vicryl-net (VN) for higher implant stability. Fifteen, 30 and 90 days after implantation, macroscopic appearance was examined, and light microscopy and immunohistology testing of the specimens were performed. Adhesions to parenchymal organs and omentum were present irrespective of the side facing the abdominal cavity. AM induced a rapid FBR, which diminished with time. Chorion (CH) and parts of the AM were resorbed within the examined period after infiltration with recipient cells and neovascularisation. The combined implant, AM, and VN showed best results because disadvantages of one material could be compensated for by the advantages of the other. The studies show that AM, in its anatomic definition, combined with VN proves to be a safe and reliable prosthetic material for the use in tissue defects.

Enhanced Bone Bonding to Nanotextured Implant Surfaces at a Short Healing Period: A Biomechanical Tensile Testing in the Rat Femur.

PubMed

Coelho, Paulo G; Zavanelli, Ricardo A; Salles, Marcos B; Yeniyol, Sinem; Tovar, Nick; Jimbo, Ryo

2016-06-01

To compare the bone bonding capabilities of 2 different surface treatments at an early healing period. Titanium alloy (Ti6Al4V) custom-made rectangular plates (1.4 × 2.4 × 4 mm) were either dual acid etched (Ti6Al4V-DAE) or DAE/nanotextured blasted (Ti6Al4V-NTB). Implants were placed in the distal femurs of 10 Wistar rats and were allowed to heal for 9 days. After euthanasia, the bone immediately proximal and distal to the implant was removed to test the bone bonding force with a universal testing machine. Ultrastructure of the bone/implant interface was assessed by scanning electron microscopy. Ti6Al4V-NTB samples exhibited significantly greater bond strength than Ti6Al4V-DAE samples. Morphologically, the Ti6Al4V-NTB surfaces presented intimate interaction with bone, whereas little interaction between the Ti6Al4V-DAE surface and bone was observed. The results of this study indicated a significant increase in bone bonding for the DAE/nanotextured blasted surface, which is suggested to be the outcome of the nanotexturing.

Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.

PubMed

Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Nakamura, Ryosuke; Otsuki, Koshi; Murono, Shigeyuki; Omori, Koichi

2017-07-01

Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

Kombucha-synthesized bacterial cellulose: preparation, characterization, and biocompatibility evaluation.

PubMed

Zhu, Changlai; Li, Feng; Zhou, Xinyang; Lin, Lin; Zhang, Tianyi

2014-05-01

Bacterial cellulose (BC) is a natural biomaterial with unique properties suitable for tissue engineering applications, but it has not yet been used for preparing nerve conduits to repair peripheral nerve injuries. The objectives of this study were to prepare and characterize the Kampuchea-synthesized bacterial cellulose (KBC) and further evaluate the biocompatibility of KBC with peripheral nerve cells and tissues in vitro and in vivo. KBC membranes were composed of interwoven ribbons of about 20-100 nm in width, and had a high purity and the same crystallinity as that of cellulose Iα. The results from light and scanning electron microscopy, MTT assay, flow cytometry, and RT-PCR indicated that no significant differences in the morphology and cell function were observed between Schwann cells (SCs) cultured on KBC membranes and glass slips. We also fabricated a nerve conduit using KBC, which was implanted into the spatium intermusculare of rats. At 1, 3, and 6 weeks post-implantation, clinical chemistry and histochemistry showed that there were no significant differences in blood counts, serum biochemical parameters, and tissue reactions between implanted rats and sham-operated rats. Collectively, our data indicated that KBC possessed good biocompatibility with primary cultured SCs and KBC did not exert hematological and histological toxic effects on nerve tissues in vivo. Copyright © 2013 Wiley Periodicals, Inc.

T-cell proliferative responses following sepsis in neonatal rats.

PubMed

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis. Copyright 2003 S. Karger AG, Basel

Effects of mechanical repetitive load on bone quality around implants in rat maxillae

PubMed Central

Uto, Yusuke; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept “bone quality”, which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones. PMID:29244883

Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

PubMed

Uto, Yusuke; Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones.

Podoplanin immunopositive lymphatic vessels at the implant interface in a rat model of osteoporotic fractures.

PubMed

Lips, Katrin Susanne; Kauschke, Vivien; Hartmann, Sonja; Thormann, Ulrich; Ray, Seemun; Kampschulte, Marian; Langheinrich, Alexander; Schumacher, Matthias; Gelinsky, Michael; Heinemann, Sascha; Hanke, Thomas; Kautz, Armin R; Schnabelrauch, Matthias; Schnettler, Reinhard; Heiss, Christian; Alt, Volker; Kilian, Olaf

2013-01-01

Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing.

Podoplanin Immunopositive Lymphatic Vessels at the Implant Interface in a Rat Model of Osteoporotic Fractures

PubMed Central

Lips, Katrin Susanne; Kauschke, Vivien; Hartmann, Sonja; Thormann, Ulrich; Ray, Seemun; Kampschulte, Marian; Langheinrich, Alexander; Schumacher, Matthias; Gelinsky, Michael; Heinemann, Sascha; Hanke, Thomas; Kautz, Armin R.; Schnabelrauch, Matthias; Schnettler, Reinhard; Heiss, Christian; Alt, Volker; Kilian, Olaf

2013-01-01

Insertion of bone substitution materials accelerates healing of osteoporotic fractures. Biodegradable materials are preferred for application in osteoporotic patients to avoid a second surgery for implant replacement. Degraded implant fragments are often absorbed by macrophages that are removed from the fracture side via passage through veins or lymphatic vessels. We investigated if lymphatic vessels occur in osteoporotic bone defects and whether they are regulated by the use of different materials. To address this issue osteoporosis was induced in rats using the classical method of bilateral ovariectomy and additional calcium and vitamin deficient diet. In addition, wedge-shaped defects of 3, 4, or 5 mm were generated in the distal metaphyseal area of femur via osteotomy. The 4 mm defects were subsequently used for implantation studies where bone substitution materials of calcium phosphate cement, composites of collagen and silica, and iron foams with interconnecting pores were inserted. Different materials were partly additionally functionalized by strontium or bisphosphonate whose positive effects in osteoporosis treatment are well known. The lymphatic vessels were identified by immunohistochemistry using an antibody against podoplanin. Podoplanin immunopositive lymphatic vessels were detected in the granulation tissue filling the fracture gap, surrounding the implant and growing into the iron foam through its interconnected pores. Significant more lymphatic capillaries were counted at the implant interface of composite, strontium and bisphosphonate functionalized iron foam. A significant increase was also observed in the number of lymphatics situated in the pores of strontium coated iron foam. In conclusion, our results indicate the occurrence of lymphatic vessels in osteoporotic bone. Our results show that lymphatic vessels are localized at the implant interface and in the fracture gap where they might be involved in the removal of lymphocytes, macrophages, debris and the implants degradation products. Therefore the lymphatic vessels are involved in implant integration and fracture healing. PMID:24130867

* A Rat Model for the In Vivo Assessment of Biological and Tissue-Engineered Valvular and Vascular Grafts.

PubMed

Sugimura, Yukiharu; Schmidt, Anna Kathrin; Lichtenberg, Artur; Assmann, Alexander; Akhyari, Payam

2017-12-01

The demand for an improvement of the biocompatibility and durability of vascular and valvular implants requires translational animal models to study the in vivo fate of cardiovascular grafts. In the present article, a review on the development and application of a microsurgical rat model of infrarenal implantation of aortic grafts and aortic valved conduits is provided. By refinement of surgical techniques and inclusion of hemodynamic considerations, a functional model has been created, which provides a modular platform for the in vivo assessment of biological and tissue-engineered grafts. Through optional addition of procalcific diets, disease-inducing agents, and genetic modifications, complex multimorbidity scenarios mimicking the clinical reality in cardiovascular patients can be simulated. Applying this model, crucial aspects of the biocompatibility, biofunctionality and degeneration of vascular and valvular implants in dependency on graft preparation, and modification as well as systemic antidegenerative treatment of the recipient have been and will be addressed.

Implantation and Recording of Wireless Electroretinogram and Visual Evoked Potential in Conscious Rats.

PubMed

Charng, Jason; He, Zheng; Bui, Bang; Vingrys, Algis; Ivarsson, Magnus; Fish, Rebecca; Gurrell, Rachel; Nguyen, Christine

2016-06-29

The full-field electroretinogram (ERG) and visual evoked potential (VEP) are useful tools to assess retinal and visual pathway integrity in both laboratory and clinical settings. Currently, preclinical ERG and VEP measurements are performed with anesthesia to ensure stable electrode placements. However, the very presence of anesthesia has been shown to contaminate normal physiological responses. To overcome these anesthesia confounds, we develop a novel platform to assay ERG and VEP in conscious rats. Electrodes are surgically implanted sub-conjunctivally on the eye to assay the ERG and epidurally over the visual cortex to measure the VEP. A range of amplitude and sensitivity/timing parameters are assayed for both the ERG and VEP at increasing luminous energies. The ERG and VEP signals are shown to be stable and repeatable for at least 4 weeks post surgical implantation. This ability to record ERG and VEP signals without anesthesia confounds in the preclinical setting should provide superior translation to clinical data.

Role of sex steroids in modulating tumor necrosis factor alpha induced changes in vascular function and blood pressure

PubMed Central

LaMarca, Babbette D.; Chandler, Derrick L.; Grubbs, Lee; Bain, Jennifer; McLemore, Gerald R.; Granger, Joey P.; Ryan, Michael J.

2007-01-01

Background We previously showed that infusion of TNF-α induces hypertension and vascular dysfunction in late pregnant but not virgin rats. In the present study we tested the hypothesis that levels of ovarian hormones to mimic pregnancy are required for TNF-α induced changes in vascular function and blood pressure in rats. Methods 21 day release pellets containing 17β-estradiol, progesterone, or both were implanted in ovariectomized (OVX) rats. Sham OVX rats were used as controls. 12 days after implantation, TNF-α or vehicle was infused via osmotic minipumps (days 12-17). On day 18, mean arterial pressure was measured and animals were sacrificed to assess vascular function. Results Average estrogen and progesterone levels across all groups were 106±6 pg/ml and 88±5 ng/ml. TNF-α was 41±7 pg/ml compared to OVX rats infused with vehicle (4±1 pg/ml). The results show that TNF-α did not cause elevated mean arterial pressure in OVX rats with increased estrogen, progesterone, both. Vascular responses to the endothelium dependent and independent agonists, acetylcholine and sodium nitroprusside, were also not changed. Phenylephrine induced contraction was moderately but significantly increased at the highest concentrations (10-4 M) only in TNF-α infused rats. Conclusion These data suggest that increased ovarian hormones to levels observed during pregnancy are not sufficient to promote TNF-α induced increases in blood pressure or vascular dysfunction. PMID:17954370

Long-term in vivo degradation behavior and near-implant distribution of resorbed elements for magnesium alloys WZ21 and ZX50.

PubMed

Amerstorfer, F; Fischerauer, S F; Fischer, L; Eichler, J; Draxler, J; Zitek, A; Meischel, M; Martinelli, E; Kraus, T; Hann, S; Stanzl-Tschegg, S E; Uggowitzer, P J; Löffler, J F; Weinberg, A M; Prohaska, T

2016-09-15

We report on the long-term effects of degrading magnesium implants on bone tissue in a growing rat skeleton using continuous in vivo micro-Computed Tomography, histological staining and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Two different magnesium alloys-one rapidly degrading (ZX50) and one slowly degrading (WZ21)-were used to evaluate the bone response and distribution of released Mg and Y ions in the femur of male Sprague-Dawley rats. Regardless of whether the alloy degrades rapidly or slowly, we found that bone recovers restitutio ad integrum after complete degradation of the magnesium implant. The degradation of the Mg alloys generates a significant increase in Mg concentration in the cortical bone near the remaining implant parts, but the Mg accumulation disappears after the implant degrades completely. The degradation of the Y-containing alloy WZ21 leads to Y enrichment in adjacent bone tissues and in newly formed bone inside the medullary space. Locally high Y concentrations suggest migration not only of Y ions but also of Y-containing intermetallic particles. However, after the full degradation of the implant the Y-enrichment disappears almost completely. Hydrogen gas formation and ion release during implant degradation did not harm bone regeneration in our samples. Magnesium is generally considered to be one of the most attractive base materials for biodegradable implants, and many magnesium alloys have been optimized to adjust implant degradation. Delayed degradation, however, generates prolonged presence in the organism with the risk of foreign body reactions. While most studies so far have only ranged from several weeks up to 12months, the present study provides data for complete implant degradation and bone regeneration until 24months, for two magnesium alloys (ZX50, WZ21) with different degradation characteristics. μCT monitoring, histological staining and LA-ICP-MS illustrate the distribution of the elements in the neighboring bony tissues during implant degradation, and reveal in particular high concentrations of the rare-earth element Yttrium. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Editorial.

PubMed

Singh, I P; Shiva, M

1994-06-01

Even though India was the first country to address population, it is behind those who came later. The government of India framed population within the context of health, but it eventually shifted the approach to health and family planning. Compartmentalism and adhoc-ism removed the programs far from the people. Eventually family welfare replaced family planning. The 8 Five Year Plan document provides a framework for appropriate, positive change in addressing the population issue. Yet, contraceptive intervention, particularly tubectomy, remains the core of population issues. In fact, tubectomy increased from about 11% of total sterilizations in the late 1960s to 96% in 1994. Women remain the target of population control. In fact, female-targeted contraceptive technology has produced IUDs, oral contraceptives, tubectomy, subdermal contraceptive implants, and the injectable contraceptive. Improvement of women's health services, their status, and their economic independence has not been attempted. Before improvement can occur, female literacy; skill development; meeting of basic needs of food, water, and health care for children to survive; and safe living and working conditions are needed. Male responsibility has risen somewhat over time. India needs to work towards a shift from contraception-oriented population control to reducing births by choice (RBBC), making RBBC a grassroots movement, a holistic approach, coordination between various government agencies, addressing demographic fundamentalism (e.g., son preference and child marriage), provision of primary health care, and equitable distribution of local and global resources. Population policy must be human.

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.

PubMed

Jin, Tao; Nicholls, Francesca J; Crum, William R; Ghuman, Harmanvir; Badylak, Stephen F; Modo, Michel

2017-01-01

Extracellular matrix (ECM) is widely used as an inductive biological scaffold to repair soft tissue after injury by promoting functional site-appropriate remodeling of the implanted material. However, there is a lack of non-invasive analysis methods to monitor the remodeling characteristics of the ECM material after implantation and its biodegradation over time. We describe the use of diamagnetic chemical exchange saturation transfer (CEST) magnetic resonance imaging to monitor the distribution of an ECM hydrogel after intracerebral implantation into a stroke cavity. In vitro imaging indicated a robust concentration-dependent detection of the ECM precursor and hydrogel at 1.8 and 3.6 ppm, which broadly corresponded to chondroitin sulfate and fibronectin. This detection was robust to changes in pH and improved at 37 °C. In vivo implantation of ECM hydrogel into the stroke cavity in a rat model corresponded macroscopically to the distribution of biomaterial as indicated by histology, but mismatches were also evident. Indeed, CEST imaging detected an endogenous "increased deposition". To account for this endogenous activity, pre-implantation images were subtracted from post-implantation images to yield a selective visualization of hydrogel distribution in the stroke cavity and its evolution over 7 days. The CEST detection of ECM returned to baseline within 3 days due to a decrease in fibronectin and chondroitin sulfate in the hydrogel. The distribution of ECM hydrogel within the stroke cavity is hence feasible in vivo, but further advances are required to warrant a selective long-term monitoring in the context of biodegradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of Piezosurgery on Bone Healing around Titanium Implants: A Histological Study in Rats.

PubMed

Sirolli, Marcelo; Mafra, Carlos Eduardo Secco; Santos, Rodrigo Albuquerque Basílio Dos; Saraiva, Luciana; Holzhausen, Marinella; César, João Batista

2016-01-01

The aim of this study was to evaluate histomorphometrically the influence of two techniques of dental implant site preparation on bone healing around titanium implants. Fifteen male Wistar rats (±300 g) were used in the study. Each tibia was randomly assigned to receive the implant site preparation either with a conventional drilling technique (control - DRILL group) or with a piezoelectric device (PIEZO group). The animals were sacrificed after 30 days and then the following histomorphometric parameters were evaluated (percentage) separately for cortical and cancellous regions: proportion of mineralized tissue (PMT) adjacent to implant threads (500 μm adjacent); bone area within the threads (BA) and bone-implant contact (BIC). The results demonstrated that there were no statistically significant differences between both groups for cancellous BIC (p>0.05) and cortical PMT (p>0.05). On the other hand, a higher percentage of BA was observed in the PIEZO group in the cortical (71.50±6.91 and 78.28±4.38 for DRILL and PIEZO groups, respectively; p<0.05) and cancellous regions (9.62±4.06 and 19.94±14.18 for DRILL and PIEZO groups, respectively; p<0.05). The piezosurgery also showed higher PMT values in the cancellous zone (9.35±5.54 and 18.72±13.21 for DRILL and PIEZO groups, respectively; p<0.05). However, the DRILL group presented better results for BIC in cortical region (80.42±10.88 and 70.25±16.93 for DRILL and PIEZO groups, respectively; p<0.05). In conclusion, for the implant site preparation, the piezosurgery was beneficial to bone healing rates in the cancellous bone region, while the drill technique produced better results in the cortical bone.

SYSTEMIC ADMINISTRATION OF KAINIC ACID INCREASES GABA LEVELS IN PERFUSATE FROM THE HIPPOCAMPUS OF RATS IN VIVO

EPA Science Inventory

The ventral hippocampi of male, Fischer-344 rats were implanted with microdialysis probes and the effects of systemically administered kainic acid (KA) (8 mg/kg, s.c.) on the in vivo release of amino acids were measured for four hours after administration. n order to measure GABA...

Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation

PubMed Central

Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

2017-01-01

Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation. PMID:28381315

Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction.

PubMed

Ingaramo, Paola I; Varayoud, Jorgelina; Milesi, María M; Schimpf, Marlise Guerrero; Muñoz-de-Toro, Mónica; Luque, Enrique H

2016-11-01

In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss. © 2016 Society for Reproduction and Fertility.

In vivo biocompatibility of three potential intraperitoneal implants.

PubMed

Defrère, Sylvie; Mestagdt, Mélanie; Riva, Raphaël; Krier, Fabrice; Van Langendonckt, Anne; Drion, Pierre; Jérôme, Christine; Evrard, Brigitte; Dehoux, Jean-Paul; Foidart, Jean-Michel; Donnez, Jacques

2011-10-10

The intraperitoneal biocompatibility of PDMS, polyHEMA and pEVA was investigated in rats, rabbits and rhesus monkeys. No inflammation was evidenced by hematological analyses and measurement of inflammatory markers throughout the experiment and by post-mortem examination of the pelvic cavity. After 3 or 6 months, histological analysis revealed fibrous tissue encapsulating PDMS and PEVA implants in all species and polyHEMA implants in rabbits and monkeys. Calcium deposits were observed inside polyHEMA implants. The intraperitoneal biocompatibility of all 3 polymers makes them suitable for the design of drug delivery systems, which may be of great interest for pathologies confined to the pelvic cavity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas.

PubMed

Ruban, Angela; Berkutzki, Tamara; Cooper, Itzik; Mohar, Boaz; Teichberg, Vivian I

2012-12-01

L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase(hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma.We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals were drinking oxaloacetate with or without injections of hGOT. In addition, mice were treated with combination treatment, which included drinking oxaloacetate with intracutaneous injections of hGOT and intraperitoneal injection of Temozolomide. Animals drinking oxaloacetate with or without injections of hGOT displayed a smaller tumor volume, reduced invasiveness and prolonged survival than control animals drinking saline. These effects were significantly enhanced by Temozolomide in mice, which increased survival by 237%. This is the first demonstration of blood Glu scavenging in brain cancer, and because of its safety, is likely to be of clinical significance for the future treatment of human gliomas. As we demonstrated, the blood glutamate scavenging treatment in combination with TMZ could be a good candidate or as an alternative treatment to the patients that do not respond to TMZ.

In Vivo Response of Laser Processed Porous Titanium Implants for Load-Bearing Implants.

PubMed

Bandyopadhyay, Amit; Shivaram, Anish; Tarafder, Solaiman; Sahasrabudhe, Himanshu; Banerjee, Dishary; Bose, Susmita

2017-01-01

Applications of porous metallic implants to enhance osseointegration of load-bearing implants are increasing. In this work, porous titanium implants, with 25 vol.% porosity, were manufactured using Laser Engineered Net Shaping (LENS™) to measure the influence of porosity towards bone tissue integration in vivo. Surfaces of the LENS™ processed porous Ti implants were further modified with TiO 2 nanotubes to improve cytocompatibility of these implants. We hypothesized that interconnected porosity created via additive manufacturing will enhance bone tissue integration in vivo. To test our hypothesis, in vivo experiments using a distal femur model of male Sprague-Dawley rats were performed for a period of 4 and 10 weeks. In vivo samples were characterized via micro-computed tomography (CT), histological imaging, scanning electron microscopy, and mechanical push-out tests. Our results indicate that porosity played an important role to establish early stage osseointegration forming strong interfacial bonding between the porous implants and the surrounding tissue, with or without surface modification, compared to dense Ti implants used as a control.

In vivo response of laser processed porous titanium implants for load-bearing implants

PubMed Central

Bandyopadhyay, Amit; Shivaram, Anish; Tarafder, Solaiman; Sahasrabudhe, Himanshu; Banerjee, Dishary; Bose, Susmita

2016-01-01

Applications of porous metallic implants to enhance osseointegration of load-bearing implants are increasing. In this work, porous titanium implants, with 25 volume% porosity, were manufactured using Laser Engineered Net Shaping (LENS™) to measure the influence of porosity towards bone tissue integration in vivo. Surfaces of the LENS™ processed porous Ti implants were further modified with TiO2 nanotubes to improve cytocompatibility of these implants. We hypothesized that interconnected porosity created via additive manufacturing will enhance bone tissue integration in vivo. To test our hypothesis, in vivo experiments using a distal femur model of male Sprague-Dawley rats were performed for a period of 4 and 10 weeks. In vivo samples were characterized via micro-computed tomography (CT), histological imaging, scanning electron microscopy, and mechanical push-out tests. Our results indicate that porosity played an important role to establish early stage osseointegration forming strong interfacial bonding between the porous implants and the surrounding tissue, with or without surface modification, compared to dense Ti implants used as a control. PMID:27307009

Sub-meninges implantation reduces immune response to neural implants.

PubMed

Markwardt, Neil T; Stokol, Jodi; Rennaker, Robert L

2013-04-15

Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. Published by Elsevier B.V.

Sub-meninges Implantation Reduces Immune Response to Neural Implants

PubMed Central

Markwardt, Neil T.; Stokol, Jodi; Rennaker, Robert L.

2013-01-01

Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. PMID:23370311

A Cell Line Producing Recombinant Nerve Growth Factor Evokes Growth Responses in Intrinsic and Grafted Central Cholinergic Neurons

NASA Astrophysics Data System (ADS)

Ernfors, Patrik; Ebendal, Ted; Olson, Lars; Mouton, Peter; Stromberg, Ingrid; Persson, Hakan

1989-06-01

The rat β nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

PubMed

Guarnieri, M; Brayton, C; Sarabia-Estrada, R; Tyler, B; McKnight, P; DeTolla, L

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

PubMed Central

Brayton, C.; Sarabia-Estrada, R.; McKnight, P.; DeTolla, L.

2017-01-01

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy. PMID:28492060

Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17 beta or diethylstilbestrol.

PubMed

Bosland, M C; Ford, H; Horton, L

1995-06-01

This study determined the incidence of prostate adenocarcinoma following long-term treatment of NBL and Sprague-Dawley rats with estradiol-17 beta or diethylstilbestrol (DES) plus testosterone and it defined the origin of these tumors. NBL and Sprague-Dawley rats were treated with two Silastic tubing implants (i.d. 1.6 mm, o.d. 3.2 mm) containing a 2 cm long filling of testosterone and one implant containing a 1 cm long filling of estradiol-17 beta or DES. Control animals received empty implants. Treated animals were killed when moribund and controls were killed at 91 (NBL) or 75 (Sprague-Dawley) weeks after initiation of treatment and accessory sex glands were sampled for histopathological examination of multiple step sections. Prostatic adenocarcinoma occurred in 100% of NBL rats after treatment with estradiol-17 beta or DES plus testosterone for 44 and 59 weeks (group means) respectively. Adenocarcinoma incidences were lower in Sprague-Dawley rats. The adenocarcinomas were small, microscopic, invasive tumors and they were spatially closely associated with the periurethral ducts of the dorsal, lateral and/or anterior (= coagulating gland) prostate, but never with the ducts of the ventral lobe and seminal vesicles. One adenocarcinoma was of uncertain origin. Duct-acinar dysplastic lesions occurred in the periphery of the dorsal and lateral prostate of all hormone-treated NBL and many Sprague-Dawley rats, but did not appear to give rise to carcinoma. Although some adenocarcinomas were contiguous with dysplastic ducts of the peripheral dorsolateral prostate, the main mass of these neoplasms was located in the periurethral area. Also, most adenocarcinomas were only connected with the periurethral ducts, in which atypical hyperplasia occurred following hormone treatment for 36 weeks or longer. Thus atypical hyperplasia of the periurethral prostate ducts, but not peripheral duct-acinar dysplasia, appeared to be the likely precursor of the induced carcinomas. Testosterone plus DES, but not estradiol-17 beta, induced marked dysplasia-like lesions in the acini of the ventral prostate of all NBL and many Sprague-Dawley rats. These lesions had progressed to carcinoma in situ (or adenoma) in 46% of NBL rats.

Preventing neuronal damage and inflammation in vivo during cortical microelectrode implantation through the use of Poloxamer P-188

NASA Astrophysics Data System (ADS)

Misra, A.; Kondaveeti, P.; Nissanov, J.; Barbee, K.; Shewokis, P.; Rioux, L.; Moxon, K. A.

2013-02-01

Objective. The aim of this study was to test the efficacy of Poloxamer P188 to reduce cell death and immune response associated with mechanical trauma to cells during implantation of a chronic recording electrode. Approach. Ceramic multi-site recording electrodes were implanted bilaterally into 15 adult male Long-Evans rats. One of each pair was randomly assigned to receive a coating of Poloxamer while the other was treated with saline. The extent of neuron loss, and glial cell recruitment were characterized at 2, 4 and 6 weeks post-implantation by stereologic analysis. Main results. At 2 and 4 weeks post-implantation, Poloxamer-coated implants showed significantly fewer glial cells and more neurons in the peri-electrode space than controls; however, this significance was lost by 6 weeks. Significance. These findings are the first to suggest that Poloxamer has neuroprotective effects in vivo; however, at a fixed loading dose, these effects are limited to approximately 1 month post-implantation.

Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

PubMed Central

Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

2016-01-01

The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

An array of highly flexible electrodes with a tailored configuration locked by gelatin during implantation-initial evaluation in cortex cerebri of awake rats.

PubMed

Agorelius, Johan; Tsanakalis, Fotios; Friberg, Annika; Thorbergsson, Palmi T; Pettersson, Lina M E; Schouenborg, Jens

2015-01-01

A major challenge in the field of neural interfaces is to overcome the problem of poor stability of neuronal recordings, which impedes long-term studies of individual neurons in the brain. Conceivably, unstable recordings reflect relative movements between electrode and tissue. To address this challenge, we have developed a new ultra-flexible electrode array and evaluated its performance in awake non-restrained animals. An array of eight separated gold leads (4 × 10 μm), individually flexible in 3D, were cut from a gold sheet using laser milling and insulated with Parylene C. To provide structural support during implantation into rat cortex, the electrode array was embedded in a hard gelatin based material, which dissolves after implantation. Recordings were made during 3 weeks. At termination, the animals were perfused with fixative and frozen to prevent dislocation of the implanted electrodes. A thick slice of brain tissue, with the electrode array still in situ, was made transparent using methyl salicylate to evaluate the conformation of the implanted electrode array. Median noise levels and signal/noise remained relatively stable during the 3 week observation period; 4.3-5.9 μV and 2.8-4.2, respectively. The spike amplitudes were often quite stable within recording sessions and for 15% of recordings where single-units were identified, the highest-SNR unit had an amplitude higher than 150 μV. In addition, high correlations (>0.96) between unit waveforms recorded at different time points were obtained for 58% of the electrode sites. The structure of the electrode array was well preserved 3 weeks after implantation. A new implantable multichannel neural interface, comprising electrodes individually flexible in 3D that retain its architecture and functionality after implantation has been developed. Since the new neural interface design is adaptable, it offers a versatile tool to explore the function of various brain structures.

Effect of exercise on the maternal outcome in pregnancy of spontaneously hypertensive rats.

PubMed

Rocha, Renato; Peraçoli, José Carlos; Volpato, Gustavo Tadeu; Damasceno, Débora Cristina; Campos, Kleber Eduardo de

2014-09-01

To evaluate the effect of exercise (swimming) on pregnancy in spontaneously hypertensive rats (SHR). Thirty three pregnant female SHR were distributed into three groups (n=11 animals/group): SHR Control=non-exercised (sedentary); SHR Ex0 = exercised from day zero to day 20 of pregnancy; and SHR Ex7 = exercised from day 7 to 20 of pregnancy. Body weight and systolic blood pressure were indirectly measured during pregnancy. On gestational day 21, the rats were anaesthetized and uterine content was withdrawn for analysis of maternal reproductive outcome parameters and fetal development. The reduced blood pressure percentage was higher in SHR Ex0 and SHR Ex7 compared to SHR Control group. Weight gain was present in all pregnancy periods, but it was lower in SHR Ex7 than in SHR Control dams. The exercise increased the pre-implantation loss rate. The post-implantation loss rate was lower in SHR Ex0 group. SHR Ex7 group showed a significantly higher percentage of fetuses classified as small for gestational age as compared to others groups. The exercise contributed to lowering gestational blood pressure in SHR rats, but had a negative impact on the developing embryo.

The effect of montelukast and antiadhesion barrier solution on the capsule formation after insertion of silicone implants in a white rat model.

PubMed

Yang, J-D; Kwon, O-H; Lee, J-W; Chung, H-Y; Cho, B-C; Park, H-Y; Kim, T-G

2013-01-01

Capsular contracture is one of the most severe complications that can occur in breast surgery following silicone implant insertion. The purpose of this study was to investigate the effect of montelukast and antiadhesion barrier solution (AABS) on reducing capsular formation and their possible synergism. This study was approved by the Animal Ethics Committee (Reference No. KNU 2012-33) and was conducted in accordance with the Kyungpook National University - Institutional Animal Care and Use Committee, Animal Ethics Committee. The experiments in this study were conducted in vivo in 4 groups of 24 rats. Following silicone implant insertion, the pocket was injected with different agents. Group I (control group) was given normal saline injections into the pocket and fed with pure water. Group II was given injections of AABS and fed with pure water. Group III was given injections of normal saline and the medication montelukast during the experimental period. Group IV was given injections of AABS and montelukast as postoperative medication. Peri-implant capsules were excised after 8 weeks and were evaluated for transparency, inflammatory cell content, capsule thickness, collagen pattern and TGF-β expression. The capsules in the experimental groups (i.e., groups II-IV) were significantly more transparent than those in group I (controls; p < 0.05, Student's t test). The mean capsule thickness of the experimental groups II (296 ± 14.76 μm), III (280 ± 14.77 μm) and IV (276 ± 39.28 μm) was smaller than that of the control group I (361 ± 35.43 μm). Compared to the control group, the histologic findings in the experimental groups suggested a decreased inflammatory response occurring in the peri-implant capsules as they exhibited minor vascularization and a reduced number of mast cells and macrophages. The collagen patterns in the experimental groups were of a lower density than in the control group with the former showing a loose, tidy collagen pattern. The amounts of TGF-β and collagen I were higher in the control group than in the experimental groups. Group IV (the synergic effect group) had a more pronounced effect on all the parameters examined than that in groups II and III with separate drug administration. Montelukast and AABS reduced the thickness, the inflammatory cell infiltrate and the myofibroblast content of the peri-implant capsules around silicone implants in this white rat model. They lowered the expression of the fibrotic mediator, TGF-β, and inhibited the peri-implant capsular fibrosis. Therefore, montelukast and AABS are effective in the reduction of silicone-induced peri-implant capsular formation.

Irradiation of intracerebral 9L gliosarcoma by a single array of microplanar x-ray beams from a synchrotron: balance between curing and sparing

NASA Astrophysics Data System (ADS)

Regnard, Pierrick; LeDuc, Géraldine; Bräuer-Krisch, Elke; Troprès, Irène; Siegbahn, Erik Albert; Kusak, Audrey; Clair, Charlotte; Bernard, Hélène; Dallery, Dominique; Laissue, Jean A.; Bravin, Alberto

2008-02-01

The purpose of this work was the understanding of microbeam radiation therapy at the ESRF in order to find the best compromise between curing of tumors and sparing of normal tissues, to obtain a better understanding of survival curves and to report its efficiency. This method uses synchrotron-generated x-ray microbeams. Rats were implanted with 9L gliosarcomas and the tumors were diagnosed by MRI. They were irradiated 14 days after implantation by arrays of 25 µm wide microbeams in unidirectional mode, with a skin entrance dose of 625 Gy. The effect of using 200 or 100 µm center-to-center spacing between the microbeams was compared. The median survival time (post-implantation) was 40 and 67 days at 200 and 100 µm spacing, respectively. However, 72% of rats irradiated at 100 µm spacing showed abnormal clinical signs and weight patterns, whereas only 12% of rats were affected at 200 µm spacing. In parallel, histological lesions of the normal brain were found in the 100 µm series only. Although the increase in lifespan was equal to 273% and 102% for the 100 and 200 µm series, respectively, the 200 µm spacing protocol provides a better sparing of healthy tissue and may prove useful in combination with other radiation modalities or additional drugs.

Isovolumic loading of the failing heart by intraventricular placement of a spring expander attenuates cardiac atrophy after heterotopic heart transplantation.

PubMed

Pokorný, Martin; Mrázová, Iveta; Šochman, Jan; Melenovský, Vojtěch; Malý, Jiří; Pirk, Jan; Červenková, Lenka; Sadowski, Janusz; Čermák, Zdeněk; Volenec, Karel; Vacková, Šárka; Maxová, Hana; Červenka, Luděk; Netuka, Ivan

2018-05-09

Cardiac atrophy is the most common complication of prolonged application of the left ventricle assist device in patients with advanced heart failure. Our aim was to evaluate the course of unloading-induced cardiac atrophy in rats with failing hearts, and to examine if increased isovolumic loading obtained by intraventricular implantation of an especially designed spring expander would attenuate this process. Heterotopic abdominal heart transplantation (HT x ) was used as a rat model of heart unloading. Heart failure (HF) was induced by volume overload achieved by creation of the aorto-caval fistula. The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart (HW) to the control heart. Isovolumic loading was increased by intraventricular implantation of a stainless steel three-branch spring expander. The course of cardiac atrophy was evaluated on days 7, 14, 21 and 28 after HT x Seven-days unloading by HT x in failing hearts sufficed to substantially decrease HW (-59 ± 3%), the decrease progressed when measured on days 14, 21 and 28 after HT x Implantation of the spring expander significantly reduced the decreases in whole HW at all the time-points (-39 ± 3 vs. -59 ± 3, -52 ± 2 vs. -69 ± 3, -51 ± 2 vs. - 71 ± 2 and -44 ± 2 vs. -71 ± 3%, respectively; p<0.05 in each case). We conclude that the enhanced isovolumic heart loading obtained by implantation of the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing rat heart. ©2018 The Author(s).

Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction.

PubMed

Sun, Cheuk-Kwan; Zhen, Yen-Yi; Leu, Steve; Tsai, Tzu-Hsien; Chang, Li-Teh; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Tan; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

2014-05-15

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hollow fibers - Their applications to the study of mammalian cell function

NASA Technical Reports Server (NTRS)

Hymer, W. C.; Angeline, M.; Harkness, J.; Chu, M.; Grindleland, R.

1984-01-01

The use of hollow fiber technology in cell culture and transplantation is examined. The morphologies of encapsulated pituitary cells before and after implantation into the rat are defined. Implantation experiments using hollow fibers to study mammalian cell functions are described. Consideration is given to examining somatotroph, prolactin, prostrate, fibroblast, and retinal cell functions. These experiments demonstrate that hollow fiber technology is applicable for studying mammalian cell functions.

Cognitive differences between male and female rats following exposure to 56Fe particles

NASA Astrophysics Data System (ADS)

Rabin, Bernard; Shukitt-Hale, Barbara; Carrihill-Knoll, Kirsty; Luskin, Katharine; Long, Lauren; Joseph, James

On exploratory class missions astronauts will be exposed to types and doses of radiation (HZE particles) that are not experienced in low earth orbit. While it is likely that the crew will consist of both male and female astronauts, there has been little research on the effects of exposure to HZE particles on cognitive performance in female subjects. While previous research has shown that exposure to HZE particles disrupts cognitive performance in male rats it remains to be established whether or not similar effects will occur with female subjects because estrogen may act as a neuroprotectant. Ovariectomized (OVX) female rats were obtained from Taconic Farms. Thirty mm segments of silastic tubing containing either 180 pg l7-estradiol/mL in sesame oil or vehicle alone were implanted subcutaneously in the neck. Three days following surgery the rats were exposed to 56Fe particles (1000 MeV/n, 0-200 cGy) at the NSRL. Following irradiation the rats were shipped to UMBC for behavioral testing. The results indicated that the pattern of decrements in cognitive performance differed between male and female rats. In addition, for female rats, there were differences in performance as a function of the presence or absence of estradiol. In the vehicle implanted subjects exposure to 56Fe particles did not affect operant responding on an ascending fixed-ratio schedule; whereas irradiation did disrupt responding in OVX animals given estradiol. These results suggest that estrogen may not be protective following exposure to HZE particles. This research was supported by Grant NNX08AM66G from NASA.

Electrophysiological studies of the feasibility of suprachoroidal-transretinal stimulation for artificial vision in normal and RCS rats.

PubMed

Kanda, Hiroyuki; Morimoto, Takeshi; Fujikado, Takashi; Tano, Yasuo; Fukuda, Yutaka; Sawai, Hajime

2004-02-01

Assessment of a novel method of retinal stimulation, known as suprachoroidal-transretinal stimulation (STS), which was designed to minimize insult to the retina by implantation of stimulating electrodes for artificial vision. In 17 normal hooded rats and 12 Royal College of Surgeons (RCS) rats, a small area of the retina was focally stimulated with electric currents through an anode placed on the fenestrated sclera and a cathode inserted into the vitreous chamber. Evoked potentials (EPs) in response to STS were recorded from the surface of the superior colliculus (SC) with a silver-ball electrode, and their physiological properties and localization were studied. In both normal and RCS rats, STS elicited triphasic EPs that were vastly diminished by changing polarity of stimulating electrodes and abolished by transecting the optic nerve. The threshold intensity (C) of the EP response to STS was approximately 7.2 +/- 2.8 nC in normal and 12.9 +/- 7.7 nC in RCS rats. The responses to minimal STS were localized in an area on the SC surface measuring 0.12 +/- 0.07 mm(2) in normal rats and 0.24 +/- 0.12 mm(2) in RCS rats. The responsive area corresponded retinotopically to the retinal region immediately beneath the anodic stimulating electrode. STS is less invasive in the retina than stimulation through epiretinal or subretinal implants. STS can generate focal excitation in retinal ganglion cells in normal animals and in those with degenerated photoreceptors, which suggests that this method of retinal stimulation is suitable for artificial vision.

Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

PubMed Central

Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

2014-01-01

Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis. PMID:25101288

Cavity Resonator Wireless Power Transfer System for Freely Moving Animal Experiments.

PubMed

Mei, Henry; Thackston, Kyle A; Bercich, Rebecca A; Jefferys, John G R; Irazoqui, Pedro P

2017-04-01

The goal of this paper is to create a large wireless powering arena for powering small devices implanted in freely behaving rodents. We design a cavity resonator based wireless power transfer (WPT) system and utilize our previously developed optimal impedance matching methodology to achieve effective WPT performance for operating sophisticated implantable devices, made with miniature receive coils (<8 mm in diameter), within a large volume (dimensions: 60.96 cm × 60.96 cm × 30 cm). We provide unique cavity design and construction methods which maintains electromagnetic performance of the cavity while promoting its utility as a large animal husbandry environment. In addition, we develop a biaxial receive resonator system to address device orientation insensitivity within the cavity environment. Functionality is demonstrated with chronic experiments involving rats implanted with our custom designed bioelectric recording device. We demonstrate an average powering fidelity of 93.53% over nine recording sessions across nine weeks, indicating nearly continuous device operation for a freely behaving rat within the large cavity resonator space. We have developed and demonstrated a cavity resonator based WPT system for long term experiments involving freely behaving small animals. This cavity resonator based WPT system offers an effective and simple method for wirelessly powering miniaturized devices implanted in freely moving small animals within the largest space.

Rapid prototyping of flexible intrafascicular electrode arrays by picosecond laser structuring.

PubMed

Mueller, Matthias; de la Oliva, Natalia; Del Valle, Jaume; Delgado-Martínez, Ignacio; Navarro, Xavier; Stieglitz, Thomas

2017-12-01

Interfacing the peripheral nervous system can be performed with a large variety of electrode arrays. However, stimulating and recording a nerve while having a reasonable amount of channels limits the number of available systems. Translational research towards human clinical trial requires device safety and biocompatibility but would benefit from design flexibility in the development process to individualize probes. We selected established medical grade implant materials like precious metals and Parylene C to develop a rapid prototyping process for novel intrafascicular electrode arrays using a picosecond laser structuring. A design for a rodent animal model was developed in conjunction with an intrafascicular implantation strategy. Electrode characterization and optimization was performed first in saline solution in vitro before performance and biocompatibility were validated in sciatic nerves of rats in chronic implantation. The novel fabrication process proved to be suitable for prototyping and building intrafascicular electrode arrays. Electrochemical properties of the electrode sites were enhanced and tested for long-term stability. Chronic implantation in the sciatic nerve of rats showed good biocompatibility, selectivity and stable stimulation thresholds. Established medical grade materials can be used for intrafascicular nerve electrode arrays when laser structuring defines structure size in the micro-scale. Design flexibility reduces re-design cycle time and material certificates are beneficial support for safety studies on the way to clinical trials.

Multi-elemental bio-imaging of rat tissue from a study investigating the bioavailability of bismuth from shotgun pellets.

PubMed

Urgast, Dagmar S; Ellingsen, Dag G; Berlinger, Balázs; Eilertsen, Einar; Friisk, Grete; Skaug, Vidar; Thomassen, Yngvar; Beattie, John H; Kwun, In-Sook; Feldmann, Jörg

2012-07-01

In recent years, bismuth has been promoted as a "green element" and is used as a substitute for the toxic lead in ammunition and other applications. However, the bioavailability and toxicity of bismuth is still not very well described. Following a hunting accident with bismuth-containing shots, a bioavailability study of bismuth from metal pellets inoculated into rat limb muscles was carried out. Bismuth could be found in urine and blood of the animals. Bio-imaging using laser ablation ICP-MS of thin sections of the tissue around the metal implant was carried out to find out more about the distribution of the metal diffusing into the tissue. Two laser ablation systems with different ablation cell designs were compared regarding their analytical performance. Low concentrations of bismuth showing a non-symmetrical pattern were detected in the tissue surrounding the metal implant. This was partly an artefact from cutting the thin sections but also bio-mobilisation of the metals of the implant could be seen. An accumulation of zinc around the implant was interpreted as a marker of inflammation. Challenges regarding sample preparation for laser ablation and bio-imaging of samples of diverse composition became apparent during the analysis.

High butter-fat diet and bisphenol A additively impair male rat spermatogenesis.

PubMed

Tarapore, Pheruza; Hennessy, Max; Song, Dan; Ying, Jun; Ouyang, Bin; Govindarajah, Vinothini; Leung, Yuet-Kin; Ho, Shuk-Mei

2017-03-01

Exposure to xenoestrogens is a probable cause of male infertility in humans. Consumption of high-fat diets and exposure to bisphenol A (BPA) is pervasive in America. Here, we test the hypothesis that gestational exposure to high dietary fats and/or BPA disrupt spermatogenesis in adulthood. Sprague-Dawley rats were fed diets containing 10kcal% butter fat (AIN), 39kcal% butter fat (HFB), or 39kcal% olive oil (HFO), with or without BPA (25μg/kg body weight/day) during pregnancy. One group of male offspring received testosterone (T)- and estradiol-17β (E2)-filled implants or sham-implants from postnatal day (PND)70-210. Another group was naturally aged to 18 months. We found that adult males with gestational exposure to BPA, HFB, or HFB+BPA, in both the aged group and the T+E2-implanted group, exhibited impairment of spermatogenesis. In contrast, gestational exposure to HFO or HFO+BPA did not affect spermatogenesis. Sham-implanted, gestational exposed groups also had normal spermatogenesis. Loss of ERα expression in round spermatids and premature expression of protamine-1 in diplotene spermatocytes were features associated with impaired spermatogenesis. Compared with the single-treatment groups, the HFB+BPA group experienced more severe effects, including atrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

PubMed Central

Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

2010-01-01

Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

Electrochemical treatment of mouse and rat fibrosarcomas with direct current

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, C.K.; McDougall, J.A.; Ahn, C.

1997-03-01

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten ratsmore » in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study; i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice, and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.« less

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats.

PubMed

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-04-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyte(TM) encapsulation devices, implanted subcutaneously and rats were monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3 ± 10.2pM that was significantly elevated over control values of 32.4 ± 2.9pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9 ± 2.3ng/ml that were significantly increased over control levels of 7.3±1.5ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with α-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of α-cells and increased islet mass. These data suggest that encapsulated transduced cells may offer a potential long term treatment of patients. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats

PubMed Central

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-01-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyteTM encapsulation devices, implanted subcutaneously and rats monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3±10.2 pM that was significantly elevated over control values of 32.4±2.9 pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9±2.3 ng/ml that were significantly increased over control levels of 7.3±1.5 ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with β-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of β-cells and increased islet mass. These data suggest encapsulated transduced cells may offer a potential long term treatment of patients. PMID:21216666

Aerobic exercise decreases the positive-reinforcing effects of cocaine.

PubMed

Smith, Mark A; Schmidt, Karl T; Iordanou, Jordan C; Mustroph, Martina L

2008-11-01

Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3mg/kg/infusion) and high (1.0mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: Prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence

PubMed Central

Burke, Andrew R.; DeBold, Joseph F.; Miczek, Klaus A.

2016-01-01

Background Activation of corticotropin releasing factor type 1 receptors (CRF-R1) in the ventral tegmental area (VTA) represents a critical mechanism for social defeat to escalate cocaine self-administration in adult rats. Objective We determined the acute effect of a CRF-R1 antagonist (CP376395) microinfusion into the VTA prior to each episode of social defeat in adolescent rats and determined whether this drug treatment could prevent later escalation of cocaine taking in early adulthood. Methods Rats were implanted with bilateral cannulae aimed at the VTA five days before the first social defeat. Bilateral microinfusion of CP376395 (500ng/side) or vehicle occurred 20 min before each episode of social defeat on postnatal days (P) 35, 38, 41, and 44. Behavior was quantified on P35 and P44. On P57, rats were implanted with intra-jugular catheters, and subsequent cocaine self-administration was analyzed. Results CP376395-treated adolescent rats walked less and were attacked more slowly, but were socially investigated more than vehicle-treated adolescents. Vehicle-treated rats showed increased social and decreased non-social exploration from P35 to P44, while CP376395-treated rats did not. Socially defeated, vehicle-treated adolescents took more cocaine during a 24-hour unlimited access binge during adulthood. The latency to supine posture on P44 was inversely correlated with later cocaine self-administration during fixed and progressive ratio schedules of reinforcement and during the binge. Conclusions CP376395 treatment in adolescence blocked escalation of cocaine taking in adulthood. Episodes of social defeat stress engender neuroadaptation in CRF-R1s in the VTA that alter coping with social stress and that persist into adulthood. PMID:27251131

Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

PubMed

Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

2014-07-01

The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

Lidocaine/ketorolac-loaded biodegradable nanofibrous anti-adhesive membranes that offer sustained pain relief for surgical wounds.

PubMed

Kao, Ching-Wei; Lee, Demei; Wu, Min-Hsuan; Chen, Jan-Kan; He, Hong-Lin; Liu, Shih-Jung

2017-01-01

The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20 days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats.

Lidocaine/ketorolac-loaded biodegradable nanofibrous anti-adhesive membranes that offer sustained pain relief for surgical wounds

PubMed Central

Kao, Ching-Wei; Lee, Demei; Wu, Min-Hsuan; Chen, Jan-Kan; He, Hong-Lin; Liu, Shih-Jung

2017-01-01

The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20 days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats. PMID:28860755

Effect of Hua Yu Xiao Zheng decoction on the expression levels of vascular endothelial growth factor and angiopoietin-2 in rats with endometriosis.

PubMed

Chen, Zhen-Zhen; Gong, Xin

2017-12-01

The aims of the present study were to investigate the effects of a traditional Chinese medicine, Hua Yu Xiao Zheng (HYXZ) decoction, on surgically induced endometriosis in a rat model and to determine the possible underlying regulatory mechanisms. A total of 108 female Sprague-Dawley rats were divided into the control group (n=12) and endometriosis group (EM group; n=96), in which endometriosis was surgically induced in model rats by autotransplantation of endometrial tissues and 72 rats survived. After 3 weeks, the EM model rats were randomly divided into four subgroups (n=18), including the untreated model group, and three groups administered 7, 14 or 21 g/kg HYXZ decoction. Following 28 days of treatment, the associated proteins and genes of ectopic endometrial tissues were analyzed using immunohistochemistry, western blotting and quantitative polymerase chain reaction to investigate the underlying mechanisms. Compared with the model group, the size of the endometriotic implants decreased significantly in the HYXZ-treated groups. Furthermore, the expression levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were significantly decreased in HYXZ-treated groups compared with the model group. These results indicate that HYXZ affected the inhibition of angiogenesis and decreased the endometriotic implant volumes and histopathological scores. The effectiveness of HYXZ may be partially attributed to the decrease of VEGF and Ang-2 expression levels in the ectopic endometrium.

Ability of mini-implant-facilitated micro-osteoperforations to accelerate tooth movement in rats.

PubMed

Cheung, Tracy; Park, Juyoung; Lee, Deborah; Kim, Catherine; Olson, Jeffrey; Javadi, Shadi; Lawson, Gregory; McCabe, James; Moon, Won; Ting, Kang; Hong, Christine

2016-12-01

Although current techniques for accelerated tooth movement often involve invasive surgical procedures, micro-osteoperforations (MOPs) using mini-implants may facilitate orthodontic tooth movement without raising flaps, reduce surgical risks, and increase patient acceptance. In this study, we evaluated the effectiveness of mini-implant-facilitated MOPs in inducing accelerated tooth movement and investigated the potential risks for root resorption. Five MOPs were placed on the left side around the maxillary first molars in 6 rats using an automated mini-implant driver, whereas the right side received no MOPs as the control. Closed-coiled springs were secured from incisors to first molars for orthodontic tooth movement. Tooth movement was measured, and samples underwent radiologic and histologic analyses. The MOP side exhibited a 1.86-fold increase in the rate of tooth movement with decreased bone density and bone volume around the first molars compared with the control side. Hematoxylin and eosin and tartrate-resistant acid phosphatase analyses showed increased numbers of osteoclasts as well as new bone formation. Three-dimensional volumetric analysis of all 5 roots of the maxillary first molars demonstrated no statistically significant difference in root volumes. Mini-implant-facilitated MOPs accelerated tooth movement without increased risk for root resorption and therefore may become a readily available and efficient treatment option to shorten orthodontic treatment time with improved patient acceptance. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

In vivo monitoring of glial scar proliferation on chronically implanted neural electrodes by fiber optical coherence tomography

PubMed Central

Xie, Yijing; Martini, Nadja; Hassler, Christina; Kirch, Robert D.; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

2014-01-01

In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation. PMID:25191264

Fracture bone healing and biodegradation of AZ31 implant in rats.

PubMed

Iglesias, C; Bodelón, O G; Montoya, R; Clemente, C; Garcia-Alonso, M C; Rubio, J C; Escudero, M L

2015-04-17

The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material.

Adipose-derived stem-cell-implanted poly(ϵ-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model.

PubMed

Zhou, Zhe; Yan, Hao; Liu, Yidong; Xiao, Dongdong; Li, Wei; Wang, Qiong; Zhao, Yang; Sun, Kang; Zhang, Ming; Lu, Mujun

2018-04-01

The study investigated the feasibility of seeding adipose-derived stem cells (ASCs) onto a poly(ϵ-caprolactone)/chitosan (PCL/CS) scaffold for bladder reconstruction using a rat model of bladder augmentation. In the experimental group, the autologous ASCs were seeded onto the PCL/CS scaffold for bladder augmentation. An unseeded scaffold was used for bladder augmentation as control group. The sham group was also set. 8 weeks after implantation, more densely smooth muscles were detected in the experimental group with a larger bladder capacity and more intensive blood vessels. Immunofluorescence staining demonstrated that some of the smooth muscle cells were transdifferentiated from the ASCs. Our findings indicated that ASC-seeded PCL/CS may be a potential scaffold for bladder tissue engineering.

Effects of cisplatin and letrozole on surgically induced endometriosis and comparison of the two medications in a rat model.

PubMed

Li, Zhanfei; Liu, Huibing; He, Zhengxing; Zhang, Guorui; Lang, Jinghe

2016-10-10

This study was to investigate the effects of cisplatin (CDDP) and letrozole on surgically induced endometriosis and comparison of the two drugs in a rat model. Endometriosis was surgically induced by autologous transplantation of endometrial pieces. Thirty model rats were divided into three groups, randomly. Group 1 (n=10) served as control and received no medication. Group 2 (n=10) received 0.2mg/kg/day of oral letrozole. Group 3 (n=10) received 35mg/m(2) CDDP via peritoneal perfusion every four days. All the rats were treated for 24days. The growth and histologic score of the implants were evaluated. The proliferation- and angiogenesis-associated proteins were assessed using immunohistochemistry and western blotting. The serum sex hormones were assayed using ELISA. After the medication, the growth and histologic score of the implants were significantly lower in the 2 and 3 groups than in the control group. The protein expressions of vascular endothelial growth factor (VEGF), aromatase P450 (P450arom), transforming growth factor-beta (TGF-β), and matrix metalloproteinase (MMP)-2, were significantly lower in groups 2 and 3 than in the control group. Further, the P450arom level was lower in the letrozole group than in the CDDP group. The TGF-β and MMP-2 levels were lower in the CDDP group than in the letrozole group. Serum T level was significantly higher in the letrozole group, and serum E2 level was lower in the letrozole group. In conclusion, cisplatin and letrozole caused similar regression of the implants in the endometriosis model rats. But their effects on the proliferation- and angiogenesis-associated protein expressions and the serum sex hormone levels were different. Cisplatin and letrozole might cause the effects in the endometriotic foci through different mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

PubMed Central

Flandreau, Elizabeth I.; Bourke, Chase H.; Ressler, Kerry J.; Vale, Wylie W.; Nemeroff, Charles B.; Owens, Michael J.

2013-01-01

Summary We have previously demonstrated that viral-mediated overexpression of corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) reproduces many of the behavioral and endocrine consequences of chronic stress. The present experiment sought to determine whether administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram reverses the adverse effects of CeA CRF overexpression. In a 2 × 2 design, adult male rats received bilateral infusions of a control lentivirus or a lentivirus in which a portion of the CRF promoter is used to drive increased expression of CRF peptide. Four weeks later, rats were then implanted with an Alzet minipump to deliver vehicle or 10 mg/kg/day escitalopram for a 4-week period of time. The defensive withdrawal (DW) test of anxiety and the sucrose-preference test (SPT) of anhedonia were performed both before and after pump implantation. Additional post-implant behavioral tests included the elevated plus maze (EPM) and social interaction (SI) test. Following completion of behavioral testing, the dexamethasone/CRF test was performed to assess HPA axis reactivity. Brains were collected and expression of HPA axis-relevant transcripts were measured using in situ hybridization. Amygdalar CRF overexpression increased anxiety-like behavior in the DW test at week eight, which was only partially prevented by escitalopram. In both CRF-overexpressing and control groups, escitalopram decreased hippocampal CRF expression while increasing hypothalamic and hippocampal expression of the glucocorticoid receptor (GR). These gene expression changes were associated with a significant decrease in HPA axis reactivity in rats treated with escitalopram. Interestingly, escitalopram increased the rate of weight gain only in rats overexpressing CRF. Overall these data support our hypothesis that amygdalar CRF is critical in anxiety-like behavior; because the antidepressant was unable to reverse behavioral manifestations of CeA CRF-OE. This may be a potential animal model to study treatment-resistant psychopathologies. PMID:23267723

In Vivo Evaluation of the Biocompatibility of Surface Modified Hemodialysis Polysulfone Hollow Fibers in Rat

PubMed Central

Sabale, Siddharth S.; Kadam, Dattatray P.; Sarkate, Laxman B.; Bellare, Jayesh R.

2011-01-01

Polysulfone (Psf) hollow fiber membranes (HFMs) have been widely used in blood purification but their biocompatibility remains a concern. To enhance their biocompatibility, Psf/TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) composite HFMs and 2-methacryloyloxyethyl phosphorylcholine (MPC) coated Psf HFMs have been prepared. They have been evaluated for in vivo biocompatibility and graft acceptance and compared with sham and commercial membranes by intra-peritoneal implantation in rats at day 7 and 21. Normal body weights, tissue formation and angiogenesis indicate acceptance of implants by the animals. Hematological observations show presence of post-surgical stress which subsides over time. Serum biochemistry results reveal normal organ function and elevated liver ALP levels at day 21. Histological studies exhibit fibroblast recruitment cells, angiogenesis and collagen deposition at the implant surface indicating new tissue formation. Immuno-histochemistry studies show non-activation of MHC molecules signifying biocompatibilty. Additionally, Psf/TPGS exhibit most favorable tissue response as compared with other HFMs making them the material of choice for HFM preparation for hemodialysis applications. PMID:22046236

Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

NASA Astrophysics Data System (ADS)

Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

2016-03-01

Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

2017-08-01

Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

Biochemical Monitoring of Spinal Cord Injury by FT-IR Spectroscopy—Effects of Therapeutic Alginate Implant in Rat Models

PubMed Central

Uckermann, Ortrud; Sitoci-Ficici, Kerim H.; Later, Robert; Beiermeister, Rudolf; Doberenz, Falko; Gelinsky, Michael; Leipnitz, Elke; Schackert, Gabriele; Koch, Edmund; Sablinskas, Valdas; Steiner, Gerald; Kirsch, Matthias

2015-01-01

Spinal cord injury (SCI) induces complex biochemical changes, which result in inhibition of nervous tissue regeneration abilities. In this study, Fourier-transform infrared (FT-IR) spectroscopy was applied to assess the outcomes of implants made of a novel type of non-functionalized soft calcium alginate hydrogel in a rat model of spinal cord hemisection (n = 28). Using FT-IR spectroscopic imaging, we evaluated the stability of the implants and the effects on morphology and biochemistry of the injured tissue one and six months after injury. A semi-quantitative evaluation of the distribution of lipids and collagen showed that alginate significantly reduced injury-induced demyelination of the contralateral white matter and fibrotic scarring in the chronic state after SCI. The spectral information enabled to detect and localize the alginate hydrogel at the lesion site and proved its long-term persistence in vivo. These findings demonstrate a positive impact of alginate hydrogel on recovery after SCI and prove FT-IR spectroscopic imaging as alternative method to evaluate and optimize future SCI repair strategies. PMID:26559822

A comparison of commercially available demineralized bone matrices with and without human mesenchymal stem cells in a rodent spinal fusion model.

PubMed

Hayashi, Tetsuo; Lord, Elizabeth L; Suzuki, Akinobu; Takahashi, Shinji; Scott, Trevor P; Phan, Kevin; Tian, Haijun; Daubs, Michael D; Shiba, Keiichiro; Wang, Jeffrey C

2016-07-01

OBJECTIVE The efficacy of some demineralized bone matrix (DBM) substances has been demonstrated in the spinal fusion of rats; however, no previous comparative study has reported the efficacy of DBM with human mesenchymal stem cells (hMSCs). There is an added cost to the products with stem cells, which should be justified by improved osteogenic potential. The purpose of this study is to prospectively compare the fusion rates of 3 different commercially available DBM substances, both with and without hMSCs. METHODS Posterolateral fusion was performed in 32 mature athymic nude rats. Three groups of 8 rats were implanted with 1 of 3 DBMs: Trinity Evolution (DBM with stem cells), Grafton (DBM without stem cells), or DBX (DBM without stem cells). A fourth group with no implanted material was used as a control group. Radiographs were obtained at 2, 4, and 8 weeks. The rats were euthanized at 8 weeks. Overall fusion was determined by manual palpation and micro-CT. RESULTS The fusion rates at 8 weeks on the radiographs for Trinity Evolution, Grafton, and DBX were 8 of 8 rats, 3 of 8 rats, and 5 of 8 rats, respectively. A significant difference was found between Trinity Evolution and Grafton (p = 0.01). The overall fusion rates as determined by micro-CT and manual palpation for Trinity Evolution, Grafton, and DBX were 4 of 8 rats, 3 of 8 rats, and 3 of 8 rats, respectively. The Trinity Evolution substance had the highest overall fusion rate, however no significant difference was found between groups. CONCLUSIONS The efficacies of these DBM substances are demonstrated; however, the advantage of DBM with hMSCs could not be found in terms of posterolateral fusion. When evaluating spinal fusion using DBM substances, CT analysis is necessary in order to not overestimate fusion.

[Changes in the activity of an epileptogenic focus in the rat hippocampus under the influence of bemitil].

PubMed

Mikhaĭlov, I B; Sharf, M Ia; Guzeva, V I

1995-01-01

Experiments performed on male rats with chronically implanted electrochemotrodes showed bemitil (12.5 and 25.0 mg/kg, intra-abdominally, 24 h prior to the locus creation) suppresses he pathological activity of (100 ED) epileptogenic locus induced by he sodium salt of penicillin in the hippocampus of the animals. Probable mechanisms of antiepileptic action of bemitil are considered.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desjardins, G.C.; Beaudet, A.; Brawer, J.R.

The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioidmore » binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.« less

Cerebral Oxygenation of the Cortex and Striatum following Normobaric Hyperoxia and Mild Hypoxia in Rats by EPR Oximetry using Multi-Probe Implantable Resonators

PubMed Central

Hou, Huagang; Li, Hongbin; Dong, Ruhong; Mupparaju, Sriram; Khan, Nadeem; Swartz, Harold

2013-01-01

Multi-site electron paramagnetic resonance (EPR) oximetry, using multi-probe implantable resonators, was used to measure the partial pressure of oxygen (pO2) in the brains of rats following normobaric hyperoxia and mild hypoxia. The cerebral tissue pO2 was measured simultaneously in the cerebral cortex and striatum in the same rats before, during, and after normobaric hyperoxia and mild hypoxia challenges. The baseline mean tissue pO2 values (±SE) were not significantly different between the cortex and striatum. During 30 min of 100% O2 inhalation, a statistically significant increase in tissue pO2 of all four sites was observed, however, the tissue pO2 of the striatum area was significantly higher than in the forelimb area of the cortex. Brain pO2 significantly decreased from the baseline value during 15 min of 15% O2 challenge. No differences in the recovery of the cerebral cortex and striatum pO2 were observed when the rats were allowed to breathe 30% O2. It appears that EPR oximetry using implantable resonators can provide information on pO2 under the experimental conditions needed for such a study. The levels of pO2 that occurred in these experiments are readily resolvable by multi-site EPR oximetry with multi-probe resonators. In addition, the ability to simultaneously measure the pO2 in several areas of the brain provides important information that could potentially help differentiate the pO2 changes that can occur due to global or local mechanisms. PMID:21445770

Cannabinoids reduce granuloma-associated angiogenesis in rats by controlling transcription and expression of mast cell protease-5

PubMed Central

De Filippis, D; Russo, A; D'Amico, A; Esposito, G; Concetta, P; Cinelli, M; Russo, G; Iuvone, T

2008-01-01

Background and purpose: Chronic inflammatory conditions, such as granulomas, are associated with angiogenesis. Mast cells represent the main cell type orchestrating angiogenesis, through the release of their granule content. Therefore, compounds able to modulate mast cell behaviour may be considered as a new pharmacological approach to treat angiogenesis-dependent events. Here, we tested the effect of selective cannabinoid (CB) receptor agonists in a model of angiogenesis-dependent granuloma formation induced by λ-carrageenin in rats. Experimental approach: Granulomas were induced by λ-carrageenin-soaked sponges implanted subcutaneously on the back of male Wistar rats. After 96 h, implants were removed and granuloma formation was measured (wet weight); angiogenesis was evaluated by histological analysis and by the measurement of haemoglobin content. Mast cells in the granulomas were evaluated histologically and by RT-PCR and immunoblotting analysis for mast cell-derived proteins (rat mast cell protease-5 (rMCP-5) and nerve growth factor). Selective CB1 and CB2 receptor agonists, ACEA and JWH-015 (0.001–0.1 mg mL−1), were given locally only once, at the time of implantation. Key results: The CB1 and CB2 receptor agonists decreased the weight and vascularization of granulomas after 96 h. This treatment also reduced mast cell number and activation in granulomatous tissue. Specifically, these compounds prevented the transcription and expression of rMCP-5, a protein involved in sprouting and advance of new blood vessels. Conclusion and implications: Modulation of mast cell function by cannabinoids reduced granuloma formation and associated angiogenesis. Therefore cannabinoid-related drugs may be useful in the management of granulomatous diseases accompanied by angiogenesis. PMID:18552882

Interleukin-6 as an early marker for fat embolism

PubMed Central

Yoga, R; Theis, JC; Walton, M; Sutherland, W

2009-01-01

Background Fat Embolism is a complication of long bone fractures, intramedullary fixation and joint arthroplasty. It may progress to fat embolism syndrome, which is rare but involves significant morbidity and can occasionally be fatal. Fat Embolism can be detected at the time of embolization by transoesophageal echocardiography or atrial blood sampling. Later, a combination of clinical signs and symptoms will point towards fat embolism but there is no specific test to confirm the diagnosis. We investigated serum Interleukin-6 (IL-6) as a possible early marker for fat embolism. Methods An animal study was conducted to simulate a hip replacement in 31 adult male Sprague Dawley rats. The procedure was performed under general anesthesia and the animals divided into 3 groups: control, uncemented and cemented. Following surgery and recovery from anaesthesia, the rats allowed to freely mobilize in their cages. Blood was taken before surgery and at 6 hours, 12 hours and 24 hours to measure serum IL-6 levels. The rats were euthanized at 24 hours and lungs removed and stained for fat. The amount of fat seen was then correlated with serum IL-6 levels. Results No rats in the control group had fat emboli. Numerous fat emboli were seen in both the uncemented and cemented implant groups. The interleukin levels were raised in all groups reaching a peak at 12 hours after surgery reaching 100 pg/ml in the control group and around 250 pg/ml in the uncemented and cemented implant groups. The IL-6 levels in the control group were significantly lower than any of the implant groups at 12 and 24 hours. At these time points, the serum IL-6 correlated with the amount of fat seen on lung histology. Conclusion Serum IL-6 is a possible early marker of fat embolism. PMID:19523233

EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

PubMed Central

Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

2013-01-01

Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

Creatine supplementation prevents hyperhomocysteinemia, oxidative stress and cancer-induced cachexia progression in Walker-256 tumor-bearing rats.

PubMed

Deminice, Rafael; Cella, Paola Sanches; Padilha, Camila S; Borges, Fernando H; da Silva, Lilian Eslaine Costa Mendes; Campos-Ferraz, Patrícia L; Jordao, Alceu Afonso; Robinson, Jason Lorne; Bertolo, Robert F; Cecchini, Rubens; Guarnier, Flávia Alessandra

2016-08-01

The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr). A life span experiment was conducted as the third experiment. Creatine was supplied in drinking water for 21 days (8 g/L) in all cases. Tumor implantation consisted of a suspension of Walker-256 cells (8.0 × 10(7) cells in 0.5 mL of PBS). The progressive increase (P < 0.05) in tumor mass coincided with a progressively lower body weight and higher hepatic oxidative stress; plasma Hcy concentration was 80 % higher (P < 0.05) by 10 days of tumor implantation. Impaired Hcy metabolism was evidenced by decreased hepatic betaine-homocysteine methyltransferase (Bhmt), glycine N-methyltransferase (Gnmt) and cystathionine beta synthase (CBS) gene expression. In contrast, creatine supplementation promoted a 28 % reduction of tumor weight (P < 0.05). Plasma Hcy (C 6.1 ± 0.6, T 10.3 ± 1.5, TCr 6.3 ± 0.9, µmol/L) and hepatic oxidative stress were lower in the TCr group compared to T. Creatine supplementation was unable to decrease Hcy concentration and to increase SAM/SAH ratio in tumor tissue. These data suggest that creatine effects on hepatic impaired Hcy metabolism promoted by tumor cell inoculation are responsible to decrease plasma Hcy in tumor-bearing rats. In conclusion, Walker-256 tumor growth is associated with progressive hyperhomocysteinemia, body weight loss and liver oxidative stress in rats. Creatine supplementation, however, prevented these tumor-associated perturbations.

Prevention of arterial graft spasm in rats using a vasodilator-eluting biodegradable nano-scaled fibre†

PubMed Central

Yagami, Kei; Yamawaki-Ogata, Aika; Satake, Makoto; Kaneko, Hiroaki; Oshima, Hideki; Usui, Akihiko; Ueda, Yuichi; Narita, Yuji

2013-01-01

OBJECTIVES Arterial graft spasm occasionally causes circulatory collapse immediately following coronary artery bypass graft. The aim of this study is to evaluate the efficacy of our developed materials, which were composed of milrinone (phosphodiesterase III inhibitor) or diltiazem (calcium-channel blocker), with nano-scaled fibre made of biodegradable polymer to prevent arterial spasm. METHODS Milrinone- or diltiazem-releasing biodegradable nano-scaled fibres were fabricated by an electrospinning procedure. In vivo milrinone- or diltiazem-releasing tests were performed to confirm the sustained release of the drugs. An in vivo arterial spasm model was established by subcutaneous injection of noradrenalin around the rat femoral artery. Rats were randomly divided into four groups as follows: those that received 5 mg of milrinone-releasing biodegradable nano-scaled fibre (group M, n = 14); 5 mg of diltiazem-releasing biodegradable nano-scaled fibre (group D, n = 12); or those that received fibre without drugs (as a control; group C, n = 14) implanted into the rat femoral artery. In the fourth group, sham operation was performed (group S, n = 10). One day after the implantation, noradrenalin was injected in all groups. The femoral arterial blood flow was measured continuously before and after noradrenalin injection. The maximum blood flow before noradrenalin injection and minimum blood flow after noradrenalin injection were measured. RESULTS In vivo drug-releasing test revealed that milrinone-releasing biodegradable nano-scaled fibre released 78% of milrinone and diltiazem-releasing biodegradable nano-scaled fibre released 50% diltiazem on the first day. The ratios of rat femoral artery blood flow after/before noradrenalin injection in groups M (0.74 ± 0.16) and D (0.72 ± 0.05) were significantly higher than those of groups C (0.54 ± 0.09) and S (0.55 ± 0.16) (P < 0.05). CONCLUSION Noradrenalin-induced rat femoral artery spasm was inhibited by the implantation of milrinone-releasing biodegradable nano-scaled fibre or diltiazem-releasing biodegradable nano-scaled fibre. These results suggested that our materials might be effective for the prevention of arterial graft spasm after coronary artery bypass graft. PMID:23513005

Synergistic effect of nanotopography and bioactive ions on peri-implant bone response

PubMed Central

Su, Yingmin; Komasa, Satoshi; Li, Peiqi; Nishizaki, Mariko; Chen, Luyuan; Terada, Chisato; Yoshimine, Shigeki; Nishizaki, Hiroshi; Okazaki, Joji

2017-01-01

Both bioactive ion chemistry and nanoscale surface modifications are beneficial for enhanced osseointegration of endosseous implants. In this study, a facile synthesis approach to the incorporation of bioactive Ca2+ ions into the interlayers of nanoporous structures (Ca-nano) formed on a Ti6Al4V alloy surface was developed by sequential chemical and heat treatments. Samples with a machined surface and an Na+ ion-incorporated nanoporous surface (Na-nano) fabricated by concentrated alkali and heat treatment were used in parallel for comparison. The bone response was investigated by microcomputed tomography assessment, sequential fluorescent labeling analysis, and histological and histomorphometric evaluation after 8 weeks of implantation in rat femurs. No significant differences were found in the nanotopography, surface roughness, or crystalline properties of the Ca-nano and Na-nano surfaces. Bone–implant contact was better in the Ca-nano and Na-nano implants than in the machined implant. The Ca-nano implant was superior to the Na-nano implant in terms of enhancing the volume of new bone formation. The bone formation activity consistently increased for the Ca-nano implant but ceased for the Na-nano implant in the late healing stage. These results suggest that Ca-nano implants have promising potential for application in dentistry and orthopedics. PMID:28184162

In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

PubMed

Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

2017-07-01

Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

In Vivo Model to Test Implanted Biosensors for Blood pH

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Somps, Chris J.; Madou, Marc; Hines, John; Wade, Charles E. (Technical Monitor)

1997-01-01

Biosensors for monitoring physiologic data continuously through telemetry are available for heart rate, respiration, and temperature but not for blood pH or ions affected by hydrogen ion concentration. A telemetric biosensor for monitoring blood pH on-line could be used to identify and manage problems in fluid and electrolyte metabolism, cardiac and respiratory function during space flight and the acid-base status of patients without the need for venipuncture in patients on Earth. Critical to the development of biosensors is a method for evaluating their performance after implantation. Mature rats, prepared with jugular, cannulas for repeated blood samples, were exposed to a gas mixture containing high levels of carbon dioxide (7%) in a closed environment to induce mild respiratory acidosis. Serial blood gas and pH measurements in venous blood were compared with electrical responses from sensors implanted in the subcutaneous tissue. Animals became slightly tachypneic after exposure to excess CO2, but remained alert and active. After 5 minutes, basal blood pH decreased from 7.404 +/- 0.013 to 7.289 +/- 0.010 (p less than 0.001)and PC02 increased from 45 +/- 6 to 65 +/- 4 mm. Hg (p les than 0.001). Thereafter pH and blood gas parameters remained stable. Implanted sensors showed a decrease in millivolts (mV) which paralleled the change in pH and averaged 5-6 mV per 0.1 unit pH. Implanted sensors remained sensitive to modest changes in tissue pH for one week. A system for inducing acidosis in rats was developed to test the in vivo performance of pH biosensors. The system provides a method which is sensitive, rapid and reproducible in the same and different animals with full recovery, for testing the performance of sensors implanted in subcutaneous tissues.

Effect of suprachiasmatic lesions on diurnal heart rate rhythm in the rat

NASA Technical Reports Server (NTRS)

Saleh, M. A.; Winget, C. M.

1977-01-01

Heart rate and locomotor activity of rats kept under 12L/12D illumination regimen were recorded every six minutes for ten days using implantable radio transmitters. Some of the rats then received bilateral RF lesions into the suprachiasmatic nucleus (SCN). Control sham operations were performed on the rest of the animals. After recovery from surgery, recording of heart rate and locomotor activity was continued for ten days. SCN-lesioned rats showed no significant diurnal fluctuation in heart rate, while normal and sham-operated rats showed the normal diurnal rhythm in that function. The arrhythmic diurnal heart-rate pattern of SCN rats appeared to be correlated with their sporadic activity pattern. The integrity of the suprachiasmatic nucleus is therefore necessary for the generation and/or expression of diurnal rhythmicity in heart rate in the rat.

Changes in pelvic organ prolapse mesh mechanical properties following implantation in rats.

PubMed

Ulrich, Daniela; Edwards, Sharon L; Alexander, David L J; Rosamilia, Anna; Werkmeister, Jerome A; Gargett, Caroline E; Letouzey, Vincent

2016-02-01

Pelvic organ prolapse (POP) is a multifactorial disease that manifests as the herniation of the pelvic organs into the vagina. Surgical methods for prolapse repair involve the use of a synthetic polypropylene mesh. The use of this mesh has led to significantly higher anatomical success rates compared with native tissue repairs, and therefore, despite recent warnings by the Food and Drug Administration regarding the use of vaginal mesh, the number of POP mesh surgeries has increased over the last few years. However, mesh implantation is associated with higher postsurgery complications, including pain and erosion, with higher consecutive rates of reoperation when placed vaginally. Little is known on how the mechanical properties of the implanted mesh itself change in vivo. It is assumed that the mechanical properties of these meshes remain unchanged, with any differences in mechanical properties of the formed mesh-tissue complex attributed to the attached tissue alone. It is likely that any changes in mesh mechanical properties that do occur in vivo will have an impact on the biomechanical properties of the formed mesh-tissue complex. The objective of the study was to assess changes in the multiaxial mechanical properties of synthetic clinical prolapse meshes implanted abdominally for up to 90 days, using a rat model. Another objective of the study was to assess the biomechanical properties of the formed mesh-tissue complex following implantation. Three nondegradable polypropylene clinical synthetic mesh types for prolapse repair (Gynemesh PS, Polyform Lite, and Restorelle) and a partially degradable polypropylene/polyglecaprone mesh (UltraPro) were mechanically assessed before and after implantation (n = 5/ mesh type) in Sprague Dawley rats for 30 (Gynemesh PS, Polyform Lite, and Restorelle) and 90 (UltraPro and Polyform Lite) days. Stiffness and permanent extension following cyclic loading, and breaking load, of the preimplanted mesh types, explanted mesh-tissue complexes, and explanted meshes were assessed using a multi-axial (ball-burst) method. The 4 clinical meshes varied from each other in weight, thickness, porosity, and pore size and showed significant differences in stiffness and breaking load before implantation. Following 30 days of implantation, the mechanical properties of some mesh types altered, with significant decreases in mesh stiffness and breaking load, and increased permanent extension. After 90 days these changes were more obvious, with significant decreases in stiffness and breaking load and increased permanent extension. Similar biomechanical properties of formed mesh-tissue complexes were observed for mesh types of different preimplant stiffness and structure after 90 days implantation. This is the first study to report on intrinsic changes in the mechanical properties of implanted meshes and how these changes have an impact on the estimated tissue contribution of the formed mesh-tissue complex. Decreased mesh stiffness, strength, and increased permanent extension following 90 days of implantation increase the biomechanical contribution of the attached tissue of the formed mesh-tissue complex more than previously thought. This needs to be considered when using meshes for prolapse repair. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.

PubMed

Alghamdi, Hamdan S; Bosco, Ruggero; Both, Sanne K; Iafisco, Michele; Leeuwenburgh, Sander C G; Jansen, John A; van den Beucken, Jeroen J J P

2014-07-01

The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions. After 4 weeks of implantation, peri-implant bone volume (%BV; by μCT) and bone area (%BA; by histomorphometry) were significantly increased within a distance of 500 μm from implant surfaces functionalized with BP compared to control implants in osteoporotic and healthy conditions. Interestingly, the deposition of nCaP/BP coatings onto implant surfaces increased both peri-implant bone contact (%BIC) and volume (%BV) compared to the deposition of nCaP or BP coatings individually, in osteoporotic and healthy conditions. The results of real-time PCR revealed similar osteogenic gene expression levels to all implant surfaces at 4-weeks post-implantation. In conclusion, simultaneous targeting of bone formation (by nCaP) and bone resorption (by BP) using nCaP/BP surface coatings represents an effective strategy for synergistically improvement of bone-implant integration, especially in osteoporotic conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening.

PubMed

Amirhosseini, Mehdi; Andersson, Göran; Aspenberg, Per; Fahlgren, Anna

2017-12-01

Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change ≥ ± 1.5 and adjusted p-value ≤ 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1β, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.

Bone marrow induced osteogenesis in hydroxyapatite and calcium carbonate implants.

PubMed

Vuola, J; Göransson, H; Böhling, T; Asko-Seljavaara, S

1996-09-01

In this experimental study, blocks of natural coral (calcium carbonate) and its structurally similar derivate in the form of hydroxyapatite (calcium phosphate) were implanted in rat latissimus dorsi muscle with autogenous bone marrow to compare their bone-forming capability. A block without marrow placed in the opposite latissimus muscle served as a control. The animals were killed at 3, 6 and 12 weeks and, in the hydroxyapatite group, also at 24 weeks. The sections were analysed histologically and histomorphometrically. Bone was found only in implants containing bone marrow. Bone formation was significantly (p < 0.05) higher in coral than in hydroxyapatite implants at 3 weeks (10.8% versus 4.8%) and at 12 weeks (13.7% versus 6.3%, bone/total original block area). At 12 weeks all the coral implants had lost their original structure, and the cross-sectional area of the block had diminished to 40% of the original area.

The osteoplastic effectiveness of the implants made of mesh titanium nickelide constructs.

PubMed

Mikhailovich Irianov, Iurii; Vladimirovna Diuriagina, Olga; Iurevna Karaseva, Tatiana; Anatolevich Karasev, Evgenii

2014-02-01

The purpose of the work was to study the features of reparative osteogenesis for filling the defect of tubular bone under implantation of mesh titanium nickelide constructs. Tibial fenestrated defect was modeled experimentally in 30 Wistar pubertal rats, followed by implant intramedullary insertion. The techniques of radiography, scanning electron microscopy and X-ray electron probe microanalysis were used. The mesh implant of titanium nickelide has been established to possess biocompatibility, osteoconductive and osteoinductive properties, the zone of osteogenesis and angiogenesis is created around it, bone cover is formed. Osteointegration of the implant occurs early, by 7 days after surgery, and by 30 days after surgery organotypical re-modelling of the regenerated bone takes place, as well as the defect is filled with lamellar bone tissue by the type of bone wound primary adhesion. By 30 days after surgery mineral content of the regenerated bone tissue approximates to the composition of intact cortex mineral phase.

Boron-Doped Nanocrystalline Diamond Electrodes for Neural Interfaces: In vivo Biocompatibility Evaluation

PubMed Central

Alcaide, María; Taylor, Andrew; Fjorback, Morten; Zachar, Vladimir; Pennisi, Cristian P.

2016-01-01

Boron-doped nanocrystalline diamond (BDD) electrodes have recently attracted attention as materials for neural electrodes due to their superior physical and electrochemical properties, however their biocompatibility remains largely unexplored. In this work, we aim to investigate the in vivo biocompatibility of BDD electrodes in relation to conventional titanium nitride (TiN) electrodes using a rat subcutaneous implantation model. High quality BDD films were synthesized on electrodes intended for use as an implantable neurostimulation device. After implantation for 2 and 4 weeks, tissue sections adjacent to the electrodes were obtained for histological analysis. Both types of implants were contained in a thin fibrous encapsulation layer, the thickness of which decreased with time. Although the level of neovascularization around the implants was similar, BDD electrodes elicited significantly thinner fibrous capsules and a milder inflammatory reaction at both time points. These results suggest that BDD films may constitute an appropriate material to support stable performance of implantable neural electrodes over time. PMID:27013949

Changes in NMR relaxation times of adjacent muscle after implantation of malignant and normal tissue.

PubMed Central

Ling, C. R.; Foster, M. A.; Mallard, J. R.

1979-01-01

In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered. PMID:526431

Necrotizing soft tissue infections (NSTIs): literary review and description of a Fournier syndrome case.

PubMed

Gubitosi, Adelmo; Moccia, Giancarlo; Ruggiero, Roberto; Docimo, Giovanni; Foroni, Fabrizio; Esposito, Emanuela; Villaccio, Giuseppe; Esposito, Alessandro; Agresti, Ettore; Agresti, Massimo

2013-01-01

A 62 y.o. male with tight fimosis, swelling, redness, pain on palpating and necrosis of the penis and scrotum was admitted in our clinic, (FGSI = 6) with periferic vasculopathy; and diabetes mellitus type II and he was in dialysis treatment before the hospitalization. The patient was HCV affected. In 24 hours he underwent radical surgical debridement with excision of all necrotic material from penis and scrotum up to the subdermal layer and tissue of doubtful viability for about 75% of the skin and circumcision. In third, fifth and seventh postoperative days he underwent to local infusion of autologous PLT growth factors. The patient was discharged in 9th postoperative day and FGSI was still 6; the skin and subdermal tissue was barely reskined, with low homogeneous granulation, edema was heavely reduced. In our case, deviation from homeostasis status at admission was the main worrying factor. We found that diabetes mellitus and renal dysfunction at admission was also important risk factor for FG. "E.Coli" was the most common organism isolated from patient wound cultures. The FGSI is an objective and easy to apply score method to quantify the metabolic status and can be used to evaluate therapeutic options and assess results.

Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

NASA Astrophysics Data System (ADS)

Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

2015-02-01

Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

Initiation and continuation of long-acting reversible contraception in the United States military healthcare system.

PubMed

Chiles, Daniel P; Roberts, Timothy A; Klein, David A

2016-09-01

Long-acting reversible contraception is more effective for pregnancy prevention than shorter-acting contraceptive methods and has the potential to reduce healthcare disparities and costs. However, long-acting reversible contraception is underused in the United States. One population of interest is beneficiaries of the United States military healthcare system who have access to universal healthcare, including no-cost, no-copay contraception with unlimited method switching, and comprise a large, actual use cohort. Efforts to increase long-acting reversible contraception initiation and continuation in this population may improve health outcomes and mitigate the profound consequences of unintended or mistimed pregnancy on readiness and cost to the military. We aimed to determine long-acting reversible contraception initiation and continuation rates among the diverse population with universal healthcare who are enrolled in the US military healthcare system. This study is a retrospective cohort of >1.7 million women, aged 14-40 years, who were enrolled in the US military healthcare system, TRICARE Prime, between October 2009 and September 2014. Individuals were assessed for long-acting reversible contraception initiation and continuation with the use of medical billing records. Method continuation and factors that were associated with early method discontinuation were evaluated with the Kaplan-Meier estimator and Cox proportional hazard models. During the study dates, 188,533 women initiated long-acting reversible contraception. Of these, 74.6% women selected intrauterine contraceptives. Method initiation rates remained relatively stable (41.7-50.1/1000 women/year) for intrauterine methods, although the rate for subdermal implants increased from 6.1-23.0/1000 women/year. In analysis of women who selected intrauterine contraceptives, 61.2% continued their method at 36 months, and 48.8% continued at 60 months. Among women who selected the implant, 32.0% continued their method at 36 months; however, 45.8% continued until 33 months (ie, 3 months before the currently recommended expiration date). Compared with intrauterine contraceptive users, implant users were more likely to discontinue their method during the 36 months after insertion (hazard ratio, 1.59; 95% confidence interval, 1.56-1.62; P < .001). Adolescents aged 14-19 years were the least likely age group to discontinue the implant before 36 months; women aged 35-40 years were the least likely to discontinue an intrauterine contraceptive before 60 months. In multivariable analysis that controlled for demographic factors and contraceptive type, early contraceptive method discontinuation was most likely among women aged 20-24 years, implant users, and women with method initiation in military clinics. In the US military healthcare system, TRICARE Prime, the initiation of long-acting reversible contraception is low but increasing, and continuation rates are high. This evidence supports long-acting reversible contraception as first-line recommendations for women of all ages who seek contraception. Published by Elsevier Inc.

An inductively powered telemetry system for temperature, EKG, and activity monitoring

NASA Technical Reports Server (NTRS)

Fryer, T. B.; Lund, G. F.; Williams, B. A.

1978-01-01

An implant telemetry system for the simultaneous monitoring of temperature, activity, and EKG from small animals, such as rats, was designed with the feature that instead of a battery the system is energized by an inductive field. A 250 kHz resonant coil surrounds the cage (30 x 30 x 20 cm) and provides the approximately 100 microns of power required to operate the implant transmitter while allowing the animal unrestrained movement in the cage. The implant can also be battery operated if desired. RF transmission is in the 8-10 MHz band, which allows the use of a simple, essentially single IC chip, receiver.

An inductively powered telemetry system for temperature, EKG, and activity monitoring

NASA Technical Reports Server (NTRS)

Fryer, T. B.; Lund, G. F.; Williams, B. A.

1978-01-01

An implant telemetry system for the simultaneous monitoring of temperature, activity, and EKG from small animals, such as rats, has recently been designed with the novel feature that instead of a battery the system is energized by an inductive field. A 250 kHz resonant coil surrounds the cage (30 x 30 x 20 cm) and provides the approximately 100 microwatt of power required to operate the implant transmitter while allowing the animal unrestrained movement in the cage. The implant can also be battery operated if desired. RF transmission is in the 8-10 MHz band, which allows the use of a simple, essentially single IC chip, receiver.

[Dihydrotestosterone improves the osseointegration of cobalt-chromium implants].

PubMed

Maus, U M; Lühmann, M; Ohnsorge, J A K; Andereya, S; Schmidt, H; Zombory, G; Siebert, C; Niedhart, C

2013-02-01

The osseointegration of actually rarely implanted cobalt-chromium implants can be critical in an elderly population. The aim of our study was to evaluate the effect of preoperative testosterone treatment on the osseointegration of cobalt-chromium implants. Press-fit implantation of 1.6 mm-diameter cobalt-chromium-molybdenum (CoCrMo) implants was performed in rats without pre-treatment in one group (n = 10) and after pre-treatment with 1 mg dihydrotestosterone (DHT) 2 days before surgery in the other group (n = 10). After 14 days, the specimens were examined by a pull-out test, histology and histomorphometry. The biomechanical testing delivered inconsistent data leading to no significant difference (6.45 ± 6.94 N vs. 4.66 ± 3.77 N). Histology showed closed contact between surrounding tissue and the implants in both groups. The bone/implant contact area was significantly enhanced after treatment with DHT (42.23 % ± 9.25 vs. 57.57 % ± 16.71, p < 0.05), while the ratio of osteoid was reduced (38.68 % ± 16.7 vs. 27.38 % ± 13.02, not significant). Pre-treatment with DHT enhances osseointegration of cobalt-chromium implants through enhanced mineralisation of peri-implant tissue. The treatment might additionally shorten postoperative rehabilitation due to its positive effects on musculature. Georg Thieme Verlag KG Stuttgart · New York.

Working Memory in Bisphenol-A Treated Middle-Aged Ovariectomized Rats

PubMed Central

Neese, Steven L.; Bandara, Suren B.; Schantz, Susan L.

2014-01-01

Over 90% of the U.S. population has detectable bisphenol-A (BPA) in their urine according to recent biomonitoring data. BPA is best known for its estrogenic properties, and most rodent research on the nervous system effects of BPA has focused on determining if chronic exposures during pre- and perinatal development have organizational effects on brain development and behavior. Estrogens also have important impacts on brain and behavior during adulthood, particularly in females during aging, but the impact of BPA on the adult brain is less studied. We have published a series of studies documenting that chronic exposure to various estrogens including 17β-estradiol, ERβ selective SERMs and soy phytoestrogens impairs performance of middle-aged female rats on an operant working memory task. The purpose of this study was to determine if chronic oral exposure to BPA would alter working memory on this same task. Ovariectomized (OVX) middle-aged Long Evans rats were tested on an operant delayed spatial alternation (DSA) task. Rats were treated for 8–10 weeks with either a 0 (vehicle control), 5 or 50 μg/kg bw/day oral bolus of BPA. A subset of the vehicle control rats were implanted with a Silastic implant containing 17β-estradiol (low physiological range) to serve as a positive control. All rats were tested for 25 sessions on the DSA task. BPA treatment did not influence performance accuracy on the DSA task, whereas 17β-estradiol significantly impaired performance, as previously reported. The results of this study suggest that chronic oral exposure to BPA does not alter working memory processes of middle-aged OVX rats assessed by this operant DSA task. PMID:23339879

Histological changes in the rat brain and spinal cord following prolonged intracerebroventricular infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients are similar to those caused by the disease.

PubMed

Gómez-Pinedo, U; Galán, L; Yañez, M; Matias-Guiu, J; Valencia, C; Guerrero-Sola, A; Lopez-Sosa, F; Brin, J R; Benito-Martin, M S; Leon-Espinosa, G; Vela-Souto, A; Lendinez, C; Guillamon-Vivancos, T; Matias-Guiu, J A; Arranz-Tagarro, J A; Barcia, J A; Garcia, A G

2018-05-01

Cerebrospinal fluid (CSF) from amyotrophic lateral sclerosis (ALS) patients induces cytotoxic effects in in vitro cultured motor neurons. We selected CSF with previously reported cytotoxic effects from 32 ALS patients. Twenty-eight adult male rats were intracerebroventricularly implanted with osmotic mini-pumps and divided into 3 groups: 9 rats injected with CSF from non-ALS patients, 15 rats injected with cytotoxic ALS-CSF, and 4 rats injected with a physiological saline solution. CSF was intracerebroventricularly and continuously infused for periods of 20 or 43days after implantation. We conducted clinical assessments and electromyographic examinations, and histological analyses were conducted in rats euthanised 20, 45, and 82days after surgery. Immunohistochemical studies revealed tissue damage with similar characteristics to those found in the sporadic forms of ALS, such as overexpression of cystatinC, transferrin, and TDP-43 protein in the cytoplasm. The earliest changes observed seemed to play a protective role due to the overexpression of peripherin, AKTpan, AKTphospho, and metallothioneins; this expression had diminished by the time we analysed rats euthanised on day 82, when an increase in apoptosis was observed. The first cellular changes identified were activated microglia followed by astrogliosis and overexpression of GFAP and S100B proteins. Our data suggest that ALS could spread through CSF and that intracerebroventricular administration of cytotoxic ALS-CSF provokes changes similar to those found in sporadic forms of the disease. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

PubMed

Hara, Y; Ogata, Y; Shirouzu, K

2000-12-01

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists.

PubMed

Kaspersen, Helge; Agmo, Anders

2012-03-01

Clinical data show that paroxetine causes sexual dysfunction in a substantial proportion of women taking this compound. This work was conducted to determine whether chronic paroxetine reduces sexual incentive motivation in female rats and whether this compound can modify any aspect of paced mating. The role of the 5-HT(1B) and 5-HT(2C) receptors in any potential effects was also evaluated. Ovariectomized female rats were implanted with osmotic minipumps releasing 10 mg/kg per day of paroxetine or vehicle for 28 days. Tests for sexual incentive motivation and paced mating were performed just before implantation and at regular intervals thereafter. The females were primed with estradiol benzoate (25 μg/rat) and progesterone (1 mg/rat) before each of these tests. On days 25-27 of treatment, the females were injected with the 5-HT(1B) antagonist GR125,743 (5 mg/kg), the 5-HT(2C) antagonist SB206,553 (5 mg/kg) and vehicle in counterbalanced order. Preinjection time was 30 min. Paroxetine reduced sexual incentive motivation on day 20 of treatment without affecting any aspect of paced mating. None of the antagonists modified the inhibitory effect of paroxetine on sexual incentive motivation. In the group chronically treated with vehicle, SB206,553 reduced proceptive behaviors in the paced mating test. No other effect was obtained. The effects of paroxetine seen in female rats are similar to those observed in women, suggesting that disturbances of sexual incentive motivation in rats are predictive of sexual dysfunction in women. The 5-HT(1B) and 5-HT(2C) receptors do not seem to be of any importance for paroxetine's inhibitory effect.

A comparison of the biocompatibility of phosphate-buffered saline and dianeal 3.86% in the rat model of peritoneal dialysis.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Breborowicz, A; Oreopoulos, D G

2001-01-01

Phosphate-buffered saline (PBS), an isotonic solution with a physiologic pH can be considered an example of a biocompatible dialysis fluid. This study compared the biocompatibility of PBS with that of Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), using a model of peritoneal dialysis in the rat. In an acute experiment, after catheter implantation, rats were infused on day 1 with PBS, on day 5 with standard dialysis solution (Dianeal 3.86%), and on day 7 again with PBS. When rats were injected with Dianeal 3.86%, the inflammatory reaction was suppressed as compared with PBS. The cell count was lower with Dianeal (-85%, p < 0.001), the neutrophil:macrophage ratio in dialysate was 80% lower (p < 0.01), total protein concentration in the Dianeal dialysate was 73% lower (p < 0.01), and the dialysate nitrite level was 45% lower (p < 0.01). In a chronic experiment, after catheter implantation, rats were dialyzed for four weeks with PBS or with Dianeal 3.86%. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed. As evaluated on a semiquantitative scale, macroscopic changes in the peritoneum were more severe in rats exposed to PBS than in those exposed to Dianeal 3.86% (8.6 +/- 3.2 vs 5.2 +/- 2.6, p < 0.05). The thickness of the visceral peritoneum was comparable in both groups; but, in PBS-treated rats, the peritoneal interstitium contained more inflammatory cells and more new vessels. During the 1-hour PET, peritoneal permeability to water and solutes was comparable in the two groups. Despite a more physiologic composition, PBS is a less biocompatible peritoneal dialysis solutions than is standard, acidic, hypertonic dialysis solution.

Working memory in bisphenol-A treated middle-aged ovariectomized rats.

PubMed

Neese, Steven L; Bandara, Suren B; Schantz, Susan L

2013-01-01

Over 90% of the U.S. population has detectable bisphenol-A (BPA) in their urine according to recent biomonitoring data. BPA is best known for its estrogenic properties, and most rodent research on the nervous system effects of BPA has focused on determining if chronic exposures during pre- and perinatal development have organizational effects on brain development and behavior. Estrogens also have important impacts on brain and behavior during adulthood, particularly in females during aging, but the impact of BPA on the adult brain is less studied. We have published a series of studies documenting that chronic exposure to various estrogens including 17β-estradiol, ERβ selective SERMs and soy phytoestrogens impairs performance of middle-aged female rats on an operant working memory task. The purpose of this study was to determine if chronic oral exposure to BPA would alter working memory on this same task. Ovariectomized (OVX) middle-aged Long Evans rats were tested on an operant delayed spatial alternation (DSA) task. Rats were treated for 8-10 weeks with either a 0 (vehicle control), 5 or 50 μg/kg bw/day oral bolus of BPA. A subset of the vehicle control rats was implanted with a Silastic implant containing 17β-estradiol (low physiological range) to serve as a positive control. All rats were tested for 25 sessions on the DSA task. BPA treatment did not influence performance accuracy on the DSA task, whereas 17β-estradiol significantly impaired performance, as previously reported. The results of this study suggest that chronic oral exposure to BPA does not alter working memory processes of middle-aged OVX rats assessed by this operant DSA task. Copyright © 2013. Published by Elsevier Inc.

Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation

PubMed Central

Cohen, D. J.; Cheng, A.; Kahn, A.; Aviram, M.; Whitehead, A. J.; Hyzy, S. L.; Clohessy, R. M.; Boyan, B. D.; Schwartz, Z.

2016-01-01

Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants. PMID:26854193

Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation.

PubMed

Cohen, D J; Cheng, A; Kahn, A; Aviram, M; Whitehead, A J; Hyzy, S L; Clohessy, R M; Boyan, B D; Schwartz, Z

2016-02-08

Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants.

Mechanical verification of soft-tissue attachment on bioactive glasses and titanium implants.

PubMed

Zhao, Desheng; Moritz, Niko; Vedel, Erik; Hupa, Leena; Aro, Hannu T

2008-07-01

Soft-tissue attachment is a desired feature of many clinical biomaterials. The aim of the current study was to design a suitable experimental method for tensile testing of implant incorporation with soft-tissues. Conical implants were made of three compositions of bioactive glass (SiO(2)-P(2)O(5)-B(2)O(3)-Na(2)O-K(2)O-CaO-MgO) or titanium fiber mesh (porosity 84.7%). The implants were surgically inserted into the dorsal subcutaneous soft-tissue or back muscles in the rat. Soft-tissue attachment was evaluated by pull-out testing using a custom-made jig 8 weeks after implantation. Titanium fiber mesh implants had developed a relatively high pull-out force in subcutaneous tissue (12.33+/-5.29 N, mean+/-SD) and also measurable attachment with muscle tissue (2.46+/-1.33 N). The bioactive glass implants failed to show mechanically relevant soft-tissue bonding. The experimental set-up of mechanical testing seems to be feasible for verification studies of soft-tissue attachment. The inexpensive small animal model is beneficial for large-scale in vivo screening of new biomaterials.

Two-generation reproductive toxicity study of implanted depleted uranium (DU) in CD rats.

PubMed

Arfsten, D P; Still, K R; Wilfong, E R; Johnson, E W; McInturf, S M; Eggers, J S; Schaeffer, D J; Bekkedal, M Y-V

2009-01-01

Depleted uranium (DU) munitions and armor plating have been used in several conflicts over the last 17 yr, including the Persian Gulf War and the Iraq War. Because of its effectiveness and availability, DU will continue to be used in military applications into the foreseeable future. There is much controversy over the use of DU in weapons and equipment because of its potential radiological and toxic hazards, and there is concern over the chronic adverse health effects of embedded DU shrapnel in war veterans and bystanders. This study evaluated the effects of long-term implantation of DU on the reproductive success of F0 generation adults and development and survival of subsequent F1 and F2 generations in a two-generation reproductive toxicity study. F0 generation Sprague-Dawley rats, 8 wk of age, were surgically implanted with 0, 4, 8, 12, or 20 DU pellets (1 x 2 mm). Inert implant control animals were implanted with 12 or 20 tantallum (Ta) pellets. The F0 generation was then mated at 120 d post DU implantation. In the F0 generation, when measured on postimplantation d 27 and 117, uranium was present in the urine of DU-implanted animals in a dose-dependent manner. F0 reproductive success was similar across treatment groups and the maternal retrieval test revealed no changes in maternal behavior. DU implantation exerted no effect on the survival, health, or well-being of the F0 generation. Necropsy results of F0 animals were negative with the exception of a marked inflammatory response surrounding the implanted DU pellets. For the F1 generation, measures of F1 development through postnatal day (PND) 20 were unremarkable and no gross abnormalities were observed in F1 offspring. No uranium was detected in whole-body homogenates of PND 4 or PND 20 pups. Necropsy findings of F1 PND 20 pups were negative and no instances of ribcage malformation were observed in F1 PND 20 pups. Body weight and body weight gain of F1 rats through PND 120 were similar across treatment groups. Eight of 414 F1 animals observed from PND 20 to 120 died of unknown causes; 7 were from litters of DU-implanted F0 mating pairs. F1 mating success at 10 wk of age was an overall 70% compared with 91% for F0 mating pairs. Mating success was similar between F1 animals derived from DU-implanted F0 adults and those derived from F0 implant control adults suggesting that the comparatively low mating success was not due to F1 DU exposure. The gestational index of F1 animals derived from mid-dose F0 mating pairs was found to be lower compared with F1 controls. The average gestation duration of F1 animals derived from high-dose F0 mating pairs was found to be significantly longer than F1 controls. F1 sperm motility analyses did not differ among experimental groups and no gross abnormalities were identified at necropsy among surviving F1 animals at PND 120. Histopathology of kidneys, spleen, thymus, bone marrow, ovaries, and testes of F1 high-dose animals did not differ from F1 controls. F1 high-dose females had significantly higher mean relative liver and heart weights compared with F1 controls; the biological relevance of this finding could not be determined. For the F2 generation, measures of F2 development through PND 20 were unremarkable and no gross abnormalities were observed in F2 offspring. Necropsy findings of F2 PND 20 pups were negative and no instances of ribcage malformation were observed in F2 PND 20 pups. Body weight and body weight gain of F2 rats through PND 90 were similar across treatment groups. Mean relative heart weights of males derived from high-dose F0 parents were significantly lower compared with F2 controls. Sperm motility and concentration analysis of F2 males at PND 90 were similar across F2 groups. Overall, the consistent absence of positive findings in this study seems to suggest that DU is not a significant reproductive or developmental hazard, particularly when one considers that mid- and high-dose rats were implanted with the equivalent of 0.3 and 0.5 lb of DU in a 70-kg human, respectively. However, the findings that seven of eight F1 adults that died postweaning were from DU-implanted F0 mating pairs, and that mean relative heart weights were elevated in high-dose F1 and F2 pups, suggest conservatism is warranted in characterizing the reproductive and teratogenic hazards of embedded DU until further studies are completed.

Biocompatibility evaluation of a thermoplastic rubber for wireless telemetric intracranial pressure sensor coating

PubMed Central

Yang, Jun; Charif, Andrea C.; Puskas, Judit E.; Phillips, Hannah; Shanahan, Kaitlyn J.; Garsed, Jessica; Fleischman, Aaron; Goldman, Ken; Luebbers, Matthew T.; Dombrowski, Stephen M.; Luciano, Mark G.

2015-01-01

This study investigated the biocompatibility of the experimental thermoplastic rubber Arbomatrix™ that will be used as the protective coating on a novel intracranial pressure (ICP) sensor silicon chip. Arbomatrix™ was benchmarked against biocompatible commercial silicone rubber shunt tubing in the brain via a rat model with 60-day implant duration. A bare silicon chip was also implanted. The results showed similar cellular distribution in the brain-implant boundary and surrounding tissues. Quantitative analysis of neuron and glia density did not show significant difference between implants. Through histological and immunohistochemical evaluation we conclude that Arbomatrix™ is well tolerated by the brain. Due to its exceptional barrier properties Arbomatrix™ has already been shown to be an excellent protective coating for new ICP monitoring chip. PMID:25688030

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barth, R.F.; Matalka, K.Z.; Bailey, M.Q.

The present study was carried out to determine the efficacy of Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma using nude rats, the human melanoma cell line MRA 27, and boronophenylalanine as the capture agent. MRA 27 cells (2 [times] 10[sup 5]) were implanted intracerebrally, and 30 days later, 120 mg of [sup 10]B-L-BPA were injected intraperitoneally into nude rats. Thirty days following implantation, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor. Six hours following administration of BPA, tumor, blood, and normal brain boron-10 levels were 23.7, 9.4, and 8.4 [mu]g/g respectively. Median survival time of untreatedmore » rats was 44 days compared to 76 days and 93 days for those receiving physical doses of 2.73 Gy and 3.64 Gy, respectively. Rats that have received both [sup 10]B-BPA and physical doses of 1.82, 2.73, or 3.64 Gy had median survival times of 170, 182, and 262 days, respectively. Forty percent of rats that had received the highest tumor dose (10.1 Gy) survived for > 300 days and in a replicate experiment 21% of the rats were longterm survivors (>220 days). Animals that received 12 Gy in a single dose or 18 Gy fractionated (2 Gy [times] 9) of gamma photons from a [sup 137]Cs source had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Histopathologic examination of the brains of longterm surviving rats, euthanized at 8 or 16 months following BNCT, showed no residual tumor, but dense accumulations of melanin laden macrophages and minimal gliosis were observed. Significant prolongations in median survival time were noted in nude rats with intracerebral human melanoma that had received BNCT, thereby suggesting therapeutic efficacy. Large animal studies should be carried out to further assess BNCT of intracerebral melanoma before any human trials are contemplated. 49 refs., 7 figs., 2 tabs.« less

Engineering bioartificial tracheal tissue using hybrid fibroblast-mesenchymal stem cell cultures in collagen hydrogels.

PubMed

Naito, Hiroshi; Tojo, Takashi; Kimura, Michitaka; Dohi, Yoshiko; Zimmermann, Wolfram-Hubertus; Eschenhagen, Thomas; Taniguchi, Shigeki

2011-02-01

We aimed at providing the first in vitro and in vivo proof-of-concept for a novel tracheal tissue engineering technology. We hypothesized that bioartificial trachea (BT) could be generated from fibroblast and collagen hydrogels, mechanically supported by osteogenically-induced mesenchymal stem cells (MSC) in ring-shaped 3D-hydrogel cultures, and applied in an experimental model of rat trachea injury. Tube-shaped tissue was constructed from mixtures of rat fibroblasts and collagen in custom-made casting molds. The tissue was characterized histologically and mechanically. Ring-shaped tissue was constructed from mixtures of rat MSCs and collagen and fused to the tissue-engineered tubes to function as reinforcement. Stiffness of the biological reinforcement was enhanced by induction of osteogeneic differentiation in MSCs. Osteogenic differentiation was evaluated by assessment of osteocalcin (OC) secretion, quantification of calcium (Ca) deposit, and mechanical testing. Finally, BT was implanted to bridge a surgically-induced tracheal defect. A three-layer tubular tissue structure composed of an interconnected network of fibroblasts was constructed. Tissue collapse was prevented by the placement of MSC-containing ring-shaped tissue reinforcement around the tubular constructs. Osteogenic induction resulted in high OC secretion, high Ca deposit, and enhanced construct stiffness. Ultimately, when BT was implanted, recipient rats were able to breathe spontaneously.

Cortical Neuroprosthesis Merges Visible and Invisible Light Without Impairing Native Sensory Function

PubMed Central

Thomson, Eric E.; Zea, Ivan; França, Wendy

2017-01-01

Abstract Adult rats equipped with a sensory prosthesis, which transduced infrared (IR) signals into electrical signals delivered to somatosensory cortex (S1), took approximately 4 d to learn a four-choice IR discrimination task. Here, we show that when such IR signals are projected to the primary visual cortex (V1), rats that are pretrained in a visual-discrimination task typically learn the same IR discrimination task on their first day of training. However, without prior training on a visual discrimination task, the learning rates for S1- and V1-implanted animals converged, suggesting there is no intrinsic difference in learning rate between the two areas. We also discovered that animals were able to integrate IR information into the ongoing visual processing stream in V1, performing a visual-IR integration task in which they had to combine IR and visual information. Furthermore, when the IR prosthesis was implanted in S1, rats showed no impairment in their ability to use their whiskers to perform a tactile discrimination task. Instead, in some rats, this ability was actually enhanced. Cumulatively, these findings suggest that cortical sensory neuroprostheses can rapidly augment the representational scope of primary sensory areas, integrating novel sources of information into ongoing processing while incurring minimal loss of native function. PMID:29279860

Assessing Anticalcification Treatments in Bioprosthetic Tissue by Using the New Zealand Rabbit Intramuscular Model

PubMed Central

Wright, Gregory A; Faught, Joelle M; Olin, Jane M

2009-01-01

The objective of this work was to demonstrate that the New Zealand White (NZW) rabbit intramuscular model can be used for detecting calcification in bioprosthetic tissue and to compare the calcification in the rabbit to that of native human valves. The rabbit model was compared with the commonly used Sprague–Dawley rat subcutaneous model. Eighteen rabbits and 18 rats were used to assess calcification in bioprosthetic tissue over time (7, 14, 30, and 90 d). The explanted rabbit and rat tissue discs were measured for calcium by using atomic absorption and Raman spectroscopy. Calcium deposits on the human valve explants were assessed by using Raman spectroscopy. The results showed that the NZW rabbit model is robust for detecting calcification in a shorter duration (14 d), with less infection complications, more space to implant tissue groups (thereby reducing animal use numbers), and a more metabolically and mechanically dynamic environment than the rat subcutaneous model . The human explanted valves and rabbit explanted tissue both showed Raman peaks at 960 cm−1 which is representative of hydroxyapatite. Hydroxyapatite is the final calcium and phosphate species in the calcification of bioprosthetic heart valves and rabbit intramuscular implants. The NZW rabbit intramuscular model is an effective model for assessing calcification in bioprosthetic tissue. PMID:19619417

The Effects of Losartan in Preserving the Structural Integrity of Decellularized Small Diameter Vascular Allograft Conduit Implants In Vivo.

PubMed

Lee, Seung Hyun; Lee, Byoung Wook; Kim, Seong Who; Choo, Suk Jung

2017-01-01

Decellularization is a proposed method of preparing nonautologous biological arterial vascular scaffolding; however, the fate of the supporting medial elastic fiber, which is important in preserving the vascular structural integrity, is uncertain. The influence of losartan on preserving the medial elastic fiber integrity in decellularized small diameter vascular conduits (SDVC) was investigated. Decellularized infrarenal abdominal aortic allografts were implanted in Sprague-Dawley rats treated either with (study rats, n = 6) or without oral losartan (control rats, n = 6) and graded 8 weeks later according to a remodeling scoring system (1-mild, 2-moderate, 3-severe) which we devised based on the intimal hyperplasia degree, morphologic changes, and elastic fiber fragmentation of the conduits. DAPI immunohistochemistry analysis was performed in 47 (25 decellularization only and 22 losartan treatment) cross-sectional slide specimens. The losartan versus decellularization only SDVC showed a significantly lower medial elastic fragmentation score (1.32 vs. 2.24, P < 0.001), superior medial layer preservation, and relatively more normal appearing intimal cellular morphology. The results suggested rats receiving decellularized SDVCs treated with losartan may yield superior medial layer elastic fiber preservation. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Controlled implant/soft tissue interaction by nanoscale surface modifications of 3D porous titanium implants.

PubMed

Rieger, Elisabeth; Dupret-Bories, Agnès; Salou, Laetitia; Metz-Boutigue, Marie-Helene; Layrolle, Pierre; Debry, Christian; Lavalle, Philippe; Vrana, Nihal Engin

2015-06-07

Porous titanium implants are widely employed in the orthopaedics field to ensure good bone fixation. Recently, the use of porous titanium implants has also been investigated in artificial larynx development in a clinical setting. Such uses necessitate a better understanding of the interaction of soft tissues with porous titanium structures. Moreover, surface treatments of titanium have been generally evaluated in planar structures, while the porous titanium implants have complex 3 dimensional (3D) architectures. In this study, the determining factors for soft tissue integration of 3D porous titanium implants were investigated as a function of surface treatments via quantification of the interaction of serum proteins and cells with single titanium microbeads (300-500 μm in diameter). Samples were either acid etched or nanostructured by anodization. When the samples are used in 3D configuration (porous titanium discs of 2 mm thickness) in vivo (in subcutis of rats for 2 weeks), a better integration was observed for both anodized and acid etched samples compared to the non-treated implants. If the implants were also pre-treated with rat serum before implantation, the integration was further facilitated. In order to understand the underlying reasons for this effect, human fibroblast cell culture tests under several conditions (directly on beads, beads in suspension, beads encapsulated in gelatin hydrogels) were conducted to mimic the different interactions of cells with Ti implants in vivo. Physical characterization showed that surface treatments increased hydrophilicity, protein adsorption and roughness. Surface treatments also resulted in improved adsorption of serum albumin which in turn facilitated the adsorption of other proteins such as apolipoprotein as quantified by protein sequencing. The cellular response to the beads showed considerable difference with respect to the cell culture configuration. When the titanium microbeads were entrapped in cell-laden gelatin hydrogels, significantly more cells migrated towards the acid etched beads. In conclusion, the nanoscale surface treatment of 3D porous titanium structures can modulate in vivo integration by the accumulative effect of the surface treatment on several physical factors such as protein adsorption, surface hydrophilicity and surface roughness. The improved protein adsorption capacity of the treated implants can be further exploited by a pre-treatment with autologous serum to render the implant surface more bioactive. Titanium microbeads are a good model system to observe these effects in a 3D microenvironment and provide a better representation of cellular responses in 3D.

Electrolytic treatment of colorectal liver tumour deposits in a rat model: a technique with potential for patients with unresectable liver tumours.

PubMed

Wemyss-Holden, S A; Robertson, G S; Hall, P D; Dennison, A R; Maddern, G J

2000-01-01

Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver 'metastases' in the rat. Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. Significant (p<0.001) tumour ablation was achieved with all electrode configurations. Tumour necrosis was more complete (p<0.05) with the electrodes positioned on either side of the tumour than with both electrodes placed in the centre of the tumour. Liver enzymes (AST and ALT) were significantly (p<0.001) elevated after treatment, but returned towards normal by 2 days. This study has shown that colorectal liver 'metastasis' can be ablated by electrolysis in a rat model. Two separate mechanisms of tumour ablation were observed: With the electrodes directly in or adjacent to the tumour, necrosis resulted from the action of cytotoxic electrode products, whereas by positioning the electrodes proximal to the tumour, necrosis was induced by a 'secondary' ischaemic effect. The findings confirm the view that electrolysis has great potential for treating patients with unresectable malignant liver tumours.

Histopathological effects of short and long-term treatment of Orchis antolica crude root extract on female albino rats fertility and pregnancy.

PubMed

Khouri, Nabil A; Daradka, Haytham

2012-02-15

The present study has investigated the effects of Orchis antolica (dose of 400 mg/kg/Body Wight) on female rats reproductive system for two time periods 4 and 12 weeks. Forty adult female Sprague-Dawley rats were divided into two treatment and two control groups of 10 rats each. The two treated groups received 400 mg/kg/body weight of Orchis antolica for two periods of 4 and 12 weeks. Female rats were allowed mating with untreated males when treatment ended. Pregnancy parameters such as: total number of pregnancy, body weight, reproductive organ weight, number of implantation sites, number of resorption sites and number of viable fetuses. The significance of these results was calculated using student's "t" and Chi- square tests. Treatment with Orchis antolica for 4 weeks did not have any significant effects on most parameters investigated except for a slight increase in the relative ovarian and embryo weights. Orchis antolica for 12 weeks induces a significant increased in the percentage of pregnancies and the number of implantation sites when compared with controls. Further, an increase in ovarian weights and in viable fetuses count was also observed. Histological sections of treated female ovaries were found to have an empty blood vessels within the cortical and modularly regions. We also noted an increased in the developing follicles at primary and secondary stages in addition to an absence of degenerative areas and increased cellularity in medulla. Long-term treatment with Orchis antolica might lead to diversified positive effects on fertility and pregnancy in female rats.

Tissue reaction to a triantibiotic paste used for endodontic tissue self-regeneration of nonvital immature permanent teeth.

PubMed

Gomes-Filho, João Eduardo; Duarte, Paulo Carvalho Tobias; de Oliveira, Claudiel Batista; Watanabe, Simone; Lodi, Carolina Simonetti; Cintra, Luciano Tavares Ângelo; Bernabé, Pedro Felício Estrada

2012-01-01

The endodontic regenerative procedure (ERP), which is an alternative to calcium hydroxide-induced apexification, involves the use of a triple antibiotic paste (TAP) as a dressing material. The aim of this study was to evaluate the response of rat subcutaneous tissue to implanted polyethylene tubes that were filled with TAP or calcium hydroxide. Thirty rats received 2 individual implants of polyethylene tubes filled with TAP or calcium hydroxide paste (CHP) and another empty tube as a control. Thirty additional rats received 2 individual implants consisting of polyethylene tubes filled with dressing material carriers (macrogol and propylene glycol) and a sham procedure. After 7, 15, 30, 60, and 90 days, 12 animals were euthanized, and the tubes and surrounding tissue were removed and processed for histology by using glycol methacrylate and stained with hematoxylin and eosin. The histological score ranged from 0 to 3 depending on the content of inflammatory cells; the fibrous capsule was considered thin or thick, and necrosis and calcification were recorded as present or absent. The results were analyzed using the Kruskal-Wallis test. Both dressing materials induced moderate reactions at 7 and 15 days. These reactions were similar to the control (P > .05) and reduced in intensity (to mild) from day 30 onward (P > .05). The carriers did not interfere with the reaction of the dressing materials. TAP and CHP were biocompatible over the different experimental periods examined. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Promoting peripheral nerve regeneration with biodegradable poly (DL-lactic acid) films

PubMed Central

Li, Ruijun; Chen, Lei; Fu, Jinling; Liu, Zhigang; Wang, Shuang; Pan, Yuehai

2015-01-01

Regeneration and repair of peripheral nerve injury has always been a major problem in the clinic. The conventional technique based on suturing the nerve ends to each other coupled with the implantation of nerve conduits outside is associated with postoperative adhesions and scar problems. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been introduced. This novel anti-adhesion film has a porous structure with better mechanical properties, better flexibility, and more controllable degradation as compared to traditional non-porous nerve conduits. However, little is known about the effects of such PDLLA films on regeneration and repair of peripheral nerve injury in vivo. In this study, we evaluated the effects of PDLLA films implantation after sciatic nerve transection and anastomosis on subsequent sciatic nerve regeneration in vivo, using a rat sciatic nerve injury model. Sciatic nerve transection surgery coupled with direct suturing only, suturing and wrapping with traditional nerve conduits, or suturing and wrapping with PDLLA films was performed on adult Wistar rats. The additional wrapping with PDLLA films inhibited the nerve adhesion after 12 weeks recovery from surgery. It also increased the compound muscle action potentials and tibialis and gastrocnemius muscle wet weight ratio following 8 weeks recovery from surgery. Regenerated nerve fibers were relatively straight and the aligned structure was complete in rats with implantations of PDLLA films. The results suggested that PDLLA films can improve the nutritional status in the muscles innervated by the damaged nerves and promote nerve regeneration in vivo. PMID:26339372